Abstract
Epilepsy is a disease of high prevalence, being well known since thousands of years as “morbus sacer.” In spite of intensive investigations, the pathophysiology of epilepsy is still poorly understood. Studies with various animal models have provided ample evidence for heterogeneity in the mechanisms of epileptogenesis. New evidence derives from investigations of kindling, which involves the delivery of brief, initially subliminal, electrical, or chemical stimuli to various areas of the brain. After 10–15 days of once-daily stimulation, the duration and intensity of afterdischarges reach a stable maximum, and a characteristic seizure is produced. Subsequent stimulation then regularly elicits seizures.
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References and Further Reading
General Considerations
Cotman CW, Iversen LL (1987) Excitatory amino acids in the brain-focus on NMDA receptors. Trends Neurosci 10:263–265
Fabene PF, Sbarbati A (2004) In vivo MRI in different models of experimental epilepsy. Curr Drug Targets 5:629–636
Fisher RS (1989) Animal models of the epilepsies. Brain Res Rev 14:245–278
Gale K (1992) GABA and epilepsy: basic concepts from preclinical research. Epilepsia 33(Suppl 5):S3–S12
Hout J, Raduoco-Thomas S, RaduocoThomas C (1973) Qualitative and quantitative evaluation of experimentally induced seizures. In: Anticonvulsant drugs, vol 1. Pergamon Press, Oxford/New York, pp 123–185
Koella WP (1985) Animal experimental methods in the study of antiepileptic drugs. In: Frey HH, Janz D (eds) Antiepileptic drugs. Handbook of experimental pharmacology, vol 74. Springer, Berlin/Heidelberg, pp 283–339
Löscher W (1997) Animal models of intractable epilepsy. Prog Neurobiol 53:239–258
Löscher W (1998) New visions in the pharmacology of anticonvulsion. Eur J Pharmacol 342:1–13
Löscher W (2002a) Animal models of drug-resistant epilepsy. Novartis Found Symp 243:149–159
Löscher W (2002b) Animal models of epilepsy for the development of antiepileptic and disease-modifying drugs. A comparison of the pharmacology of kindling and poststatus epilepticus models of temporal epilepsy. Epilepsy Res 50:105–123
Löscher W, Schmidt D (1988) Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 2:145–181
MacDonald RL, McLean MJ (1986) Anticonvulsant drugs: mechanisms of action. Adv Neurol 44:713–736
Meldrum BS (1986) Pharmacological approaches to the treatment of epilepsy. In: Meldrum BS, Porter RJ (eds) New anticonvulsant drugs. John Libbey, London/Paris, pp 17–30
Meldrum BS (1989) GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br J Pharmacol 27:3S–11S
Porter RJ, Rogawski MA (1992) New antiepileptic drugs: from serendipity to rational discovery. Epilepsia 33(Suppl 1):S1–S6
Rogawski MA, Porter RJ (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev 42:223–286
Rump S, Kowalczyk M (1987) Effects of antiepileptic drugs in electrophysiological tests. Pol J Pharmacol Pharm 39:557–566
Smyth MD, Barbaro NM, Baraban SC (2002) Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res 50:251–264
Swinyard EA (1973) Assay of antiepileptic drug activity in experimental animals: standard tests. In: Anticonvulsant drugs, vol 1. Pergamon Press, Oxford/New York, pp 47–65
Toman JEP, Everett GM (1964) Anticonvulsants. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities: pharmacometrics. Academic, London/New York, pp 287–300
Watkins JC, Olverman HJ (1987) Agonists and antagonists for excitatory amino acid receptors. Trends Neurosci 10:265–272
Woodbury DM (1972) Applications to drug evaluations. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 557–583
GABAB Receptor Binding
Fonnum F (1987) Biochemistry, anatomy, and pharmacology of GABA neurons. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 173–182
Lloyd KG, Morselli PL (1987) Psychopharmacology of GABAergic drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York pp 183–195
3H-GABA Uptake in Rat Cerebral Cortex Synaptosomes
Brehm L et al (1979) GABA uptake inhibitors and structurally related “pro-drugs”. In: Krogsgaard-Larsen P et al (eds) GABA-neurotransmitters. Academic, New York, pp 247–261
Fjalland B (1978) Inhibition by neuroleptics of uptake of3H GABA into rat brain synaptosomes. Acta Pharmacol Toxicol 42:73–76
Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation. J Anat (Lond) 96:79–88
Iversen LL, Bloom FE (1972) Studies of the uptake of3HGABA and3H-glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography. Brain Res 41:131–143
Korgsgaard-Larsen P (1985) GABA agonist and uptake inhibitors. Research Biochemicals Incorporated – Neurotransmissions 1
Meldrum B et al (1982) GABA-uptake inhibitors as anticonvulsant agents. In: Okada Y, Roberts E (eds) Problems in GABA research from brain to bacteria. Excerpta Medica, Princeton, pp 182–191
Roberts E (1974) γ-Aminobutyric acid and nervous system function – a perspective. Biochem Pharmacol 23:2637–2649
Roskoski R (1978) Net uptake of l-glutamate and GABA by high affinity synaptosomal transport systems. J Neurochem 31:493–498
Ryan L, Roskoski R (1977) Net uptake of γ-Aminobutyric acid by a high affinity synaptosomal transport system. J Pharm Exp Ther 200:285–291
Snodgrass SR (1990) GABA and GABA neurons: Controversies, problems, and prospects. In: Receptor site analysis. NEN, pp 23–33
Tapia R (1975) Blocking of GABA uptake. In: Iversen I, Iversen S, Snyder S (eds) Handbook of psychopharmacology, vol 4. Plenum Press, New York, pp 33–34
GABA Uptake and Release in Rat Hippocampal Slices
Akaike N, Moorhouse AJ (2003) Techniques: applications of the nerve-bouton preparation in neuropharmacolgy. Trends Pharmacol Sci 24:44–47
Akaike N, Muarkami N, Katsurabayashi S, Jin YH, Imazawa T (2002) Focal stimulation of single GABAergic presynaptic boutons on the rat hippocampus neuron. Neurosci Res 42:187–195
Drewe JA, Childs GV, Kunze DL (1988) Synaptic transmission between dissociated adult mammalian neurons and attached synaptic boutons. Science 241:1810–1813
Falch E, Larsson OM, Schousboe A, Krogsgard-Larsen P (1990) GABA-A agonists and GABA uptake inhibitors. Drug Dev Res 21:169–188
Haage D, Karlsson U, Johansson S (1998) Heterogeneous presynaptic Ca2+ channel types triggering GABA release onto medial preoptic neurons from rat. J Physiol (Lond) 507:77–91
Huger FP, Smith CP, Chiang Y, Glamkowski EJ, Ellis DB (1987) Pharmacological evaluation of HP 370, a potential atypical anti-psychotic agent. 2. in vitro profile. Drug Dev Res 11:169–175
Jang IS, Rhee JS, Watanabe T, Akaike N, Akaike N (2001) Histaminergic modulation of GABAergic transmission in rat ventromedial hypothalamic neurons. J Physiol (Lond) 534:791–803
Kishimoto K, Koyama S, Akaike N (2001) Synergistic μ-opioid and 5-HT1A presynaptic inhibition of GABA release in rat periaqueductal gray neurons. Neuropharmacology 41:529–538
Koyama S, Kubo C, Rhee JS, Akaike N (1999) Presynaptic serotonergic inhibition of GABAergic synaptic transmission in mechanically dissociated rat basolateral amygdala neurons. J Physiol (Lond) 518:525–538
Lajtha A, Sershen H (1975) Inhibition of amino acid uptake by the absence of Na+ in slices of brain. J Neurochem 24:667–672
Lüddens H, Korpi ER (1995) Biological function of GABAA/ benzodiazepine receptor heterogeneity. J Psychiat Res 29:77–94
Möhler H (1992) GABAergic synaptic transmission. Arzneim Forsch/Drug Res 42:211–214
Nilsson M, Hansson E, Rönnbäck L (1990) Transport of valproate and its effects on GABA uptake in astroglial primary culture. Neurochem Res 15:763–767
Nilsson M, Hansson E, Rönnbäck L (1992) Interactions between valproate, glutamate, aspartate, and GABA with respect to uptake in astroglial primary cultures. Neurochem Res 17:327–332
Rhee JS, Ishibashi H, Akaike N (1999) Calcium channels in the GABAergic presynaptic nerve terminals projecting to Meynert neurons of the rat. J Neurochem 72:800–806
Roskoski R (1978) Net uptake of l-glutamate and GABA by high affinity synaptosomal transport systems. J Neurochem 31:493–498
Suzdak PD, Jansen JA (1995) A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia 36:612–626
Taylor CP (1990) GABA receptors and GABAergic synapses as targets for drug development. Drug Dev Res 21:151–160
Taylor CP, Vartanian MG, Schwarz RD, Rock DM, Callahan MJ, Davis MD (1990) Pharmacology of CI-966: a potent GABA uptake inhibitor, in vitro and in experimental animals. Drug Dev Res 21:195–215
Vorobjev VS (1991) Vibrodissociation of sliced mammalian nervous tissue. J Neurosci Methods 38:145–150
Walton NY, Gunnawan S, Treiman DM (1994) Treatment of experimental status epilepticus with the GABA uptake inhibitor, tiagabine. Epilepsy Res 19:237–244
Glutamate Receptors: [3H]CPP Binding
Becker J, Li Z, Noe CR (1998) Molecular and pharmacological characterization of recombinant rat/mice N-methyl-d-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae. Eur J Biochem 256:427–435
Bettler B, Mulle C (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacol 34:123–139
Bräuner-Osboren H, Egebjerg J, Nielsen NØ, Madsen U, Krogsgaard-Larsen P (2000) Ligands for glutamate receptors: design and therapeutic properties. J Med Chem 43:2609–2645
Carlsson M, Carlsson A (1990) Interactions between glutaminergic and monoaminergic systems within the basal ganglia – implications for schizophrenia and Parkinson’s disease. Trends Neurosci 13:272–276
Carter C, Rivy JP, Scatton B (1989) Ifenprodil and SL 82.0715 are antagonists at the polyamine site of the N-methyl-d-aspartate (NMDA) receptor. Eur J Pharmacol 164:611–612
Chimirri A, Gitto R, Zappala M (1999) AMPA receptor antagonists. Expert Opin Ther Pat 9:557–570
Chittajallu R, Braithwaite SP, Clarke VRJ, Henley JM (1999) Kainate receptors: subunits, synaptic localization and function. Trends Pharmacol Sci 20:26–35
Clarke VRJ, Ballyk BA, Hoo KH, Mandelzys A, Pellizari A, Bath CP, Thomas J, Sharpe EF, Davies CH, Ornstein PL, Schoepp DD, Kamboj RK, Collingridge GL, Lodges D, Bleakman D (1997) A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature 389:599–603
Collingridge GL, Lester RAJ (1989) Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 40:143–210
Cotman CW, Iversen LL (1987) Excitatory amino acids in the brain-focus on NMDA receptors. Trends Neurosci 10:263–265
Cunningham MD, Ferkany JW, Enna SH (1994) Excitatory amino acid receptors: a gallery of new targets for pharmacological intervention. Life Sci 54:135–148
Danysz W, Parsons CG (1998) Glycine and N-methyl-d-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev 50:597–664
Davies J, Evans RH, Herrling PL, Jones AW, Olverman HJ, Pook P, Watkins JC (1986) CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]D-AP5 binding sites on brain membranes and anticonvulsant activity. Brain Res 382:169–173
Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61
Dunn RW, Corbett R, Martin LL, Payack JF, Laws-Ricker L, Wilmot CA, Rush DK, Cornfeldt ML, Fielding S (1990) Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists. Current and future trends in anticonvulsant, anxiety, and stroke therapy. Wiley-Liss, pp 495–512
Ferkany J, Coyle JT (1986) Heterogeneity of sodium-dependent excitatory amino acid uptake mechanisms in rat brain. J Neurosci Res 16:491–503
Fleck AW, Bahring R, Patneau DK, Mayer ML (1996) AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide. J Neurophysiol 75:2322–2333
Fletcher EJ, Lodge D (1995) New developments in the molecular pharmacology of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainate receptors. Pharmacol Ther 70:65–89
Foster AC, Fagg GE (1984) Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors. Brain Res Rev 7:103–164
Foster AC, Fagg GE (1987) Comparison of l-[3H]glutamate, d-[3H]aspartate, DL-[3H]AP5 and [3H]NMDA as ligands for NMDA receptors in crude postsynaptic densities from rat brain. Eur J Pharmacol 133:291–300
Gallo V, Ghiani CA (2000) Glutamate receptors in glia: new cells, new inputs and new functions. Trends Pharmacol Sci 21:252–258
Harris EW, Ganong AH, Monaghan DT, Watkins JC, Cotman CW (1986) Action of 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP): a new and highly potent antagonist of N-methyl-d-aspartate receptors in the hippocampus. Brain Res 382:174–177
Hatt H (1999) Modification of glutamate receptor channels: molecular mechanisms and functional consequences. Naturwissenschaften 86:177–186
Herrling PL (1994) Clinical implications of NMDA receptors. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 376–394
Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108
Honoré T, Lauridsen J, Krogsgaard-Larsen P (1982) The binding of [3H]AMPA, a structural analogue of glutamic acid to rat brain membranes. J Neurochem 38:173–178
Honoré T, Davies SN, Drejer J, Fletchner EJ, Jacobsen P, Lodge D, Nielsen FE (1988) Quinoxalidinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241:701–703
Hu RQ, Koh S, Togerson T, Cole AJ (1998) Neuronal stress and injury in C57/BL mice after systemic kainate administration. Brain Res 810:229–240
Huettner JE (2003) Kainate receptors and synaptic transmission. Prog Neurobiol 70:387–407
Iversen LL, Kemp JA (1994) Non-competitive NMDA antagonists as drugs. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 469–486
Jones SM, Snell LD, Johnson KM (1989) Characterization of the binding of radioligands to the N-methyl-d-aspartate, phenylcyclidine and glycine receptors in buffy coat membranes. J Pharmacol Methods 21:161–168
Kemp JA, McKernan RM (2002) NMDA receptor pathways as drug targets. Nat Neurosci Suppl 5:1039–1042
Kemp JA, Foster AC, Wong EHF (1987) Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci 10:294–298
Kodama M, Yamada M, Sato K, Kitamura Y, Koyama F, Sato T, Morimoto K, Kuroda S (1999) Effects of YM90K, a selective AMP receptor antagonist, on amygdala-kindling and long-term hippocampal potentiation in rats. Eur J Pharmacol 374:11–19
Kohara A, Okada M, Tsutsumi R, Ohno K, Takahashi M, Shimizu-Sasamata M, Shishikura JI, Inami H, Sakamoto S, Yamaguchi T (1998) In vitro characterization of YM872, a selective, potent and highly water-soluble α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor antagonist. J Pharm Pharmacol 50:795–801
Lees GJ (2000) Pharmacology of AMPA/kainate receptor ligands and their therapeutic potential in neurological and psychiatric disorders. Drug 59:33–78
Lehmann J, Schneider J, McPherson S, Murphy DE, Bernard P, Tsai C, Bennett DA, Pastor G, Steel DJ, Boehm C, Cheney DL, Liebman JM, Williams M, Wood PL (1987) CPP, a selective N-methyl-d-aspartate (NMDA)-type receptor antagonist: characterization in vitro and in vivo. J Pharmacol Exp Ther 240:737–746
Lehmann J, Hutchison AJ, McPherson SE, Mondadori C, Schmutz M, Sinton CM, Tsai C, Murphy DE, Steel DJ, Williams M, Cheney DL, Wood PL (1988) CGS 19755, a selective and competitive N-methyl-d-aspartate type excitatory amino acid receptor antagonist. J Pharmacol Exp Ther 246:65–75
Loftis JM, Janowsky A (2003) The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther 97:55–85
London ED, Coyle JT (1979) Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol 15:492–505
Löscher W (1998) Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy. Prog Neurobiol 54:721–741
Lynch G (2004) AMPA receptor modulators as cognitive enhancers. Curr Opin Pharmacol 4:4–11
Mayer ML, Armstrong N (2004) Structure and function of glutamate receptor ion channels. Annu Rev Physiol 66:161–181
Mayer ML, Westbrook GL (1987) The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28:197–276
Mayer ML, Benveniste M, Patneau DK (1994) NMDA receptor agonists and competitive antagonists. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 132–146
Meldrum BS (1998) The glutamate synapse as a therapeutic target: perspectives for the future. Prog Brain Res 116:441–458
Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 130(4S Suppl):1007S–1015S
Meldrum BS, Chapman AG (1994) Competitive NMDA antagonists as drugs. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 457–468
Monaghan DT, Buller AL (1994) Anatomical, pharmacological, and molecular diversity of native NMDA receptor subtypes. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 158–176
Monaghan DT, Cotman CW (1982) The distribution of [3H]kainic acid binding sites in rat CNS as determined by autoradiography. Brain Res 252:91–100
Monaghan DT, Bridges RJ, Cotman CW (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 29:365–402
Mukhin A, Kovaleva ES, London ED (1997) Two affinity states of N-methyl-d-aspartate recognition sites: modulation by cations. J Pharmacol Exp Ther 282:945–954
Murphy DE, Schneider J, Boehm C, Lehmann J, Williams M (1987a) Binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to rat brain membranes: a selective, high-affinity ligand for N-methyl-d-aspartate receptors. J Pharmacol Exp Ther 240:778–784
Murphy DE, Snowhill EW, Williams M (1987b) Characterization of quisqualate recognition sites in rat brain tissue using DL-[3H]α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and a filtration assay. Neurochem Res 12:775–782
Murphy DE, Hutchinson AJ, Hurt SD, Williams M, Sills MA (1988) Characterization of the binding of [3H]-CGS 19755, a novel N-methyl-d-aspartate antagonist with nanomolar affinity in rat brain. Br J Pharmacol 95:932–938
Mutel V, Trube G, Klingelschmidt A, Messer J, Bleuel Z, Humbel U, Clifford MM, Ellis GJ, Richards JG (1998) Binding characteristics of a potent AMPA receptor antagonist [3H]Ro 48–8587 in rat brain. J Neurochem 71:418–426
Nakanishi S (1992) Molecular diversity of glutamate receptors and implication for brain function. Science 258:593–603
Nielsen EO, Varming T, Mathiesen C, Jensen LH, Moller A, Gouliaev AH, Watjen F, Drejer J (1999) SPD 502: a water-soluble and in vivo long-lasting AMPA antagonist with neuroprotective activity. J Pharmacol Exp Ther 289:1492–1501
Olney JW (1990) Excitotoxic amino acids and neuropsychiatric disorders. Annu Rev Pharmacol Toxicol 30:47–71
Olsen RW, Szamraj O, Houser CR (1987) [3H]AMPA binding to glutamate receptor subpopulations in rat brain. Brain Res 402:243–254
Olverman JH, Monaghan DT, Cotman CW, Watkins JC (1986) [3H]CPP, a new competitive ligand for NMDA receptors. Eur J Pharmacol 131:161–162
Parsons CG, Danysz W, Quack G (1998) Glutamate in CNS disorders as a target for drug development. Drug News Perspect 11:523–569
Piotrovsky LB, Garyaev AP, Poznyakova LN (1991) Dipeptide analogues of N-acetylaspartylglutamate inhibit convulsive effects of excitatory amino acids in mice. Neurosci Lett 125:227–230
Rogawski MA, Porter RJ (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with considerations of promising developmental stage compounds. Pharmacol Rev 42:223–286
Tauboll E, Gjerstad L (1998) Effects of antiepileptic drugs on the activation of glutamate receptors. Prog Brain Res 116:385–393
Thomsen C (1997) The L-AP4 receptor. Gen Pharmacol 29:151–158
Toms NJ, Reid ME, Phillips W, Kemp MC, Roberts PJ (1997) A novel kainate receptor ligand [3H]-(2S,4R)-4-methylglutamate. Pharmacological characterization in rabbit brain membranes. Neuropharmacology 36:1483–1488
Wahl P, Frandsen A, Madsen U, Schousboe A, Krogsgaard-Larsen P (1998) Pharmacology and toxicology of ATOA, an AMPA receptor antagonist and a partial agonist at GluR5 receptors. Neuropharmacology 37:1205–1210
Watkins JC (1994) The NMDA receptor concept: origins and development. In: Collingridge GL, Watkins JC (eds) The NMDA receptor, 2nd edn. Oxford University Press, Oxford, pp 1–30
Watkins JC, Olverman HJ (1987) Agonists and antagonists for excitatory amino acid receptors. Trends Neurosci 10:265–272
Willis CL, Wacker DA, Bartlett RD, Bleakman D, Lodge D, Chamberlin AR, Bridges RJ (1997) Irreversible inhibition of high affinity [3H]kainate binding by a photoactivatable analogue: (2′S,3′S,4′R)-2′-carboxy-4′-(2-diazo-1-oxo-3,3,3-trifluoropropyl)-3′-pyrrolidinyl acetate. J Neurochem 68:1503–1510
Worms P, Willigens MT, Lloyd KG (1981) The behavioral effects of systemically administered kainic acid: a pharmacological analysis. Life Sci 29:2215–2225
Young AB, Fagg GE (1990) Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 11:126–133
Zeman S, Lodge D (1992) Pharmacological characterization of non-NMDA subtypes of glutamate receptor in the neonatal rat hemidissected spinal cord in vitro. Br J Pharmacol 106:367–372
Zhou L-L, Gu ZQ, Costa AM, Yamada KA, Mansson PE, Giordano T, Skolnick P, Jones KA (1997) (2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high affinity ligand for kainate receptors. J Pharmacol Exp Ther 280:422–427
NMDA Receptor Complex: [3H]TCP Binding
Abe T, Sugihara H, Nawa H, Shigemoto R, Mizuno N, Nakanishi S (1992) Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem 267:13361–13368
Bashir ZI, Bortolotto ZA, Davies CH, Berretta M, Irving AJ, Seal AJ, Henley AM, Jane DE, Watkins JC, Collingridge GL (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363:347–350
Bednar B, Cunningham ME, Kiss L, Cheng G, McCauley JA, Liverton NJ, Koblan KS (2004) Kinetic characterization of novel NR2B antagonists using fluorescence detection of calcium flux. J Neurosci Methods 137:247–255
Chenard BL, Menniti FS (1999) Antagonists selective for NMDA receptors containing the NR2B subunit. Curr Pharm Res 5:381–404
Cotman CW, Iversen LL (1987) Excitatory amino acids in the brain-focus on NMDA receptors. Trends Neurosci 10:263–265
Dannhardt G, von Gruchalla M, Elben U (1994) Tools for NMDA-receptor elucidation: synthesis of spacer-coupled MK-801 derivatives. Pharm Pharmacol Lett 4:12–15
Dunn RW, Corbett R, Martin LL, Payack JF, Laws-Ricker L, Wilmot CA, Rush DK, Cornfeldt ML, Fielding S (1990) Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists. Current and future trends in anticonvulsant, anxiety, and stroke therapy. Wiley-Liss, pp 495–512
Ebert B, Madsen U, Lund TM, Lenz SM, Krogsgaard-Larsen P (1994) Molecular pharmacology of the AMPA agonist, (S)-2-amino-3-(3-hydroxy-5-phenyl-4-isoxazolyl)propionic acid [(S)-APPA] and the AMPA antagonist, (R)-APPA. Neurochem Int 24:507–515
Fischer G, Mutel V, Trube G, Malherbe P, Kew JNC, Mohacsi E, Heitz MP, Kemp JA (1997) Ro 25–6981, a highly potent and selective blocker of N-methyl-d-aspartate receptors containing the NRB2 subunit. J Pharmacol Exp Ther 283:1285–1292
Goldman ME, Jacobson AE, Rice KC, Paul SM (1985) Differentiation of [3H]phencyclidine and (+)-[3H]SKΒ-10,047 binding sites in rat cerebral cortex. FEBS Lett 190:333–336
Grimwood S, ILe Bourdellès B, Atack JR, Barton C, Cockettt W, Cook SM, Gilbert E, Hutson PH, McKernan RM, Myers J, Ragan CI, Wingrove PB, Whiting PJ (1996) Generation and characterization of stable cell lines expressing recombinant human N-methyl-d-aspartate receptor subtypes. J Neurochem 66:2239–2247
Hansen JJ, Krogsgaard-Larsen P (1990) Structural, conformational, and stereochemical requirements of central excitatory amino acid receptors. Med Res Rev 10:55–94
Ishii T, Moriyoshi K, Sugihara H, Sakurada K, Kadotani H, Yokoi M, Akazawa C, Shigemoto R, Mizuno N, Masu M, Nakanishi S (1993) Molecular characterization of the family of N-methyl-d-aspartate receptor subunits. J Biol Chem 268:2836–2843
Iversen LL (1994) MK-801 (Dizocilpine maleate) – NMDA receptor antagonist. Neurotransmission 10(1):1–4
Javitt DC, Zukin SR (1989) Biexponential kinetics of [3H]MK-801 binding: evidence for access to closed and open N-methyl-d-aspartate receptor channels. Mol Pharmacol 35:387–393
Johnson KM, Jones SM (1990) Neuropharmacol of phencyclidine: basic mechanisms and therapeutic potential. Annu Rev Pharmacol Toxicol 30:707–750
Keinänen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH (1990) A family of AMPA-selective glutamate receptors. Science 249:556–560
Kemp JA, Foster AC, Wong EHF (1987) Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci 10:294–298
Kew JNC, Trube G, Kemp JA (1998) State-dependent NMDA receptor antagonism by Ro 8–4304, a novel NR2B selective, non-competitive, voltage-independent antagonist. Br J Pharmacol 123:463–472
Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushyia E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M, Mishina M (1992) Molecular diversity of the NMDA receptor channel. Nature 358:36–41
Loo P, Braunwalder A, Lehmann J, Williams M (1986) Radioligand binding to central phencyclidine recognition sites is dependent on excitatory amino acid receptor agonists. Eur J Pharmacol 123:467–468
Loo PS, Braunwalder AF, Lehmann J, Williams M, Sills MA (1987) Interaction of l-glutamate and magnesium with phencyclidine recognition sites in rats brain: evidence for multiple affinity states of the phencyclidine/N-methyl-d-aspartate receptor complex. Mol Pharmacol 32:820–830
Maragos WF, Chu DCM, Greenamyre T, Penney JB, Young AB (1986) High correlation between the localization of [3H]TCP binding and NMDA receptors. Eur J Pharmacol 123:173–174
Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349:760–765
Meguro H, Mori H, Araki K, Kushiya E, Katsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357:70–74
Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221
Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354:31–37
Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi N (1993) Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for l-2-amino-4-phosphonobutyrate. J Biol Chem 268:11868–11873
Nowak G, Remond A, McNamara M, Paul IA (1995) Swim stress increases the potency of glycine at the N-methyl-d-aspartate receptor complex. J Neurochem 64:925–927
Reyes M, Reyes A, Opitz T, Kapin MA, Stanton PK (1998) Eliprodil, a non-competitive, NR2B-selective NMDA antagonist, protects pyramidal neurons in hippocampal slides from hypoxic/ischemic damage. Brain Res 782:212–218
Reynolds IJ, Miller RJ (1988) Multiple sites for the regulation of the N-methyl-d-aspartate receptor. Mol Pharmacol 33:581–584
Rogawski MA, Porter RJ (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with considerations of promising developmental stage compounds. Pharmacol Rev 42:223–286
Sacaan AI, Johnson KM (1989) Spermine enhances binding to the glycine site associated with the N-methyl-d-aspartate receptor complex. Mol Pharmacol 36:836–839
Schoepp D, Bockaert J, Sladeczek F (1990) Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. Trends Pharmacol Sci 11:508–515
Sills MA, Fagg G, Pozza M, Angst C, Brundish DE, Hurt SD, Wilusz EJ, Williams M (1991) [3H]CGP 39653: a new N-methyl-d-aspartate antagonist radioligand with low nanomolar affinity in rat brain. Eur J Pharmacol 192:19–24
Simon RP, Swan JH, Griffiths T, Meldrum BS (1984) Blockade of N-methyl-d-aspartate receptors may protect against ischemic damage in the brain. Science 226:850–852
Snell LD, Morter RS, Johnson KM (1987) Glycine potentiates N-methyl-d-aspartate-induced [3H]TCP binding to rat cortical membranes. Neurosci Lett 83:313–320
Snell LD, Morter RS, Johnson KD (1988) Structural requirements for activation of the glycine receptor that modulates the N-methyl-d-aspartate operated ion channel. Eur J Pharmacol 156:105–110
Sugihara H, Moriyoshi K, Ishii T, Masu M, Nakanishi S (1992) Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing. Biochem Biophys Res Commun 185:826–832
Tanabe Y, Nomura A, Masu M, Shigemoto R, Mizuno N, Nakanishi S (1993) Signal transduction, pharmacological properties, and expression patterns of two metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci 13:1372–1378
Thedinga KH, Benedict MS, Fagg GE (1989) The N-methyl-d-aspartate (NMDA) receptor complex: a stoichiometric analysis of radioligand binding domains. Neurosci Lett 104:217–222
Thomson AM (1989) Glycine modulation of the NMDA receptor/channel complex. Trends Neurosci 12:349–353
Vignon J, Chicheportiche R, Chicheportiche M, Kamenka JM, Geneste P, Lazdunski M (1983) [3H]TPC: a new tool with high affinity to the PCP receptor in rat brain. Brain Res 280:194–197
Watkins JC, Olverman HJ (1987) Agonists and antagonists for excitatory amino acid receptors. Trends Neurosci 10:265–272
Watkins JC, Krogsgaard-Larsen P, Honoré T (1990) Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci 11:25–33
Williams K, Romano C, Molinoff PB (1989) Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-d-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. Mol Pharmacol 36:575–581
Wong EHF, Kemp JA (1991) Sites for antagonism on the N-methyl-d-aspartate receptor channel complex. Annu Rev Pharmacol Toxicol 31:401–425
Wong EHF, Knight AR, Woodruff GN (1988) [3H]MK-801 labels a site on the N-methyl-d-aspartate receptor channel complex in rat brain membranes. J Neurochem 50:274–281
Yoneda Y, Ogita K (1991) Neurochemical aspects of the N-methyl-d-aspartate receptor complex. Neurosci Res 10:1–33
Metabotropic Glutamate Receptors
Acher FC, Tellier FJ, Azerad R, Brabet IN, Fagni L, Pin JPR (1997) Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J Med Chem 40:3119–3129
Alexander S, Peters J, Mathie A, MacKenzie G, Smith A (2001) TiPS nomenclature supplement
Annoura H, Fukunaga A, Uesugi M, Tatsuoka T, Horikawa Y (1996) A novel class of antagonists for metabotropic glutamate receptors, 7-(hydroxyimino)-cyclopropa[b]chromenla-carboxylates. Bioorg Med Chem Lett 6:763–766
Attwell PJE, Singh-Kent N, Jane D, Croucher MJ, Bradford HF (1998) Anticonvulsant and glutamate release-inhibiting properties of the highly potent metabotropic glutamate receptor agonist (2S,2′ R,3′R)-2-(2′ 3′ dicarboxycyclopropyl)-glycine (DCG-IV). Brain Res 805:138–143
Bedingfield JS, Jane DE, Kemp MC, Toms NJ, Roberts PJ (1996) Novel potent selective phenylglycine antagonists of metabotropic glutamate receptors. Eur J Pharmacol 309:71–78
Berridge MJ, Downes CP, Hanley MR (1982) Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206:587–595
Brauner-Osborne H, Nielsen B, Krogsgaard-Larsen P (1998) Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. Eur J Pharmacol 350:311–316
Bruno V, Battaglia G, Copani A, Casabona G, Storto M, di Giorgi-Gerevini V, Ngomba R, Nicoletti F (1998) Metabotropic glutamate receptors and neurodegeneration. Prog Brain Res 116:209–221
Cartmell J, Adam G, Chaboz S, Henningsen R, Kemp JA, Klingelschmidt A, Metzler V, Monsma F, Schaffhauser H, Wichmann J, Mutel V (1998) Characterization of [3H](2S,2′R,3′R)-2-(2′, 3′-dicarboxycyclopropyl)glycine ([3H]DCG IV) binding to metabotropic mGlu2 receptor transfected cell membranes. Br J Pharmacol 123:497–504
Christoffersen GRJ, Christensen LH, Hammer P, Vang M (1999) The class I metabotropic glutamate receptor antagonist, AIDA, improves short-term and impairs long-term memory in a spatial task for rats. Neuropharmacology 38:817–823
Conn PJ (2003) Physiological roles and therapeutic potential of metabotropic glutamate receptors. Ann N Y Acad Sci 1003:12–21
Conn PJ, Pin JP (1997) Pharmacology and function of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237
DeBlasi A, Conn PJ, Pin JP, Nicolette F (2001) Molecular determinants of metabotropic glutamate signaling. Trends Pharmacol Sci 22:114–120
Doherty AJ, Palmer MJ, Henley JM, Collingridge GL, Jane DE (1997) (R, S)-2-chloro-5-hydroxyphenylglycine (CHPG) activates mGlu5, but not mGlu1, receptors expressed in CHO cells and potentiates NMDA responses in the hippocampus. Neuropharmacology 36:265–267
Eriksen L, Thomsen C (1995) [3H]-l-2-amino-4-phosphonobutyrate labels a metabotropic glutamate receptor, mGluR4a. Br J Pharmacol 116:3279–3287
Gasparini F, Bruno V, Battaglia G, Lukic S, Leonhardt T, Inderbitzin W, Laurie D, Sommer B, Varney MA, Hess SD, Johnson EC, Kuhn R, Urwyler S, Sauer D, Portet C, Schmutz M, Nicoletti F, Flor PJ (1999) (R, S)-4-Phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo. J Pharmacol Exp Ther 289:1678–1687
Gssparini F, Kuhn R, Pin JP (2002) Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol 2:43–49
Helton DR, Tizzano JP, Monn JA, Schoepp DD, Kallman MJ (1998) Anxiolytic and side-effect profile of LY354740: a potent and highly selective, orally active agonist for group II metabotropic glutamate receptors. J Pharmacol Exp Ther 284:651–660
Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108
Ishida M, Akagi H, Shimamoto K, Ohfune Y, Shinozaki H (1990) A potent metabotropic glutamate receptor agonist: electrophysiological actions of a conformationally restricted glutamate analogue in the rat spinal cord and Xenopus oocytes. Brain Res 537:311–314
Ishida M, Saitoh T, Nakamura Y, Kataoka K, Shinozaki H (1994) A novel metabotropic glutamate receptor agonist: (2S,1′ S,2′ R,3′R)-2-(carboxy-3-methoxymethylcyclopropyl)glycine (cis-MCG-I). Eur J Pharmacol Mol Pharmacol Sect 268:267–270
Jane D, Doherty A (2000) Muddling through the mGlu maze? Tocris Rev 13
Jane DE, Jones PLSJ, Pook PCK, Tse HW, Watkins JC (1994) Actions of two new antagonists showing selectivity for different subtypes of metabotropic glutamate receptor in the neonatal spinal cord. Br J Pharmacol 112:809–816
Kingston AE, Ornstein PL, Wright RA, Johnson BG, Mayne NG, Burnett JP, Belagaje R, Wu S, Schoepp DD (1998) LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Neuropharmacology 37:1–12
Knöpfel T, Kuhn R, Allgeier H (1995) Metabotropic glutamate receptors: novel targets for drug development. J Med Chem 38:1417–1425
Knöpfel T, Madge T, Nicoletti F (1996) Metabotropic glutamate receptors. Expert Opin Ther Pat 6:1061–1067
Konieczny J, Ossowska K, Wolfarth S, Pilc A (1998) LY354740, a group II metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats. Naunyn-Schmiedeberg’s Arch Pharmacol 358:500–502
Monn JA, Valli MJ, Massey SM, Hansen MM, Kress TJ, Wepsiec JP, Harkness AR, Grutsch JL Jr, Wright PA, Johnson PG, Andis SL, Kingston A, Tomlinson R, Lewis R, Griffey KR, Tizzano JP, Schoepp DD (1999) Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J Med Chem 42:1027–1040
Nakanishi S, Masu M (1994) Molecular diversity and function of glutamate receptors. Annu Rev Biophys Biomol Struct 23:319–348
Nicoletti F, Bruno V, Copani A, Casabona G, Knöpfel T (1996) Metabotropic glutamate receptors: a new target for the treatment of neurodegenerative disorders? Trends Neurosci 19:267–271
Okamoto N, Hori S, Akazawa C, Hayashi Y, Shigemoto R, Mizuno N, Nakanishi S (1994) Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction. J Biol Chem 269:1231–1236
Ornstein PL, Arnold MB, Bleisch TJ, Wright RA, Wheeler WJ, Schoepp DD (1998) [3H]LY341495, a highly potent, selective and novel radioligand for labeling group II metabotropic glutamate receptors. Bioorg Med Chem Lett 8:1919–1922
Pin JP, Acher F (2002) The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord 1:297–317
Pin JP, Duvoisin R (1995) The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34:1–26
Porter RHP, Briggs RSJ, Roberts PJ (1992) l-Aspartate-β-hydroxamate exhibits mixed agonist/antagonist activity at the glutamate metabotropic receptor in rat neonatal cerebrocortical slices. Neurosci Lett 144:87–89
Riedel G, Reymann KG (1996) Metabotropic glutamate receptors in hippocampal long-term potentiation and learning and memory. Acta Physiol Scand 157:1–19
Schaffhauser H, Richards JG, Cartmell J, Chaboz S, Kemp JA, Klingelschmidt A, Messer J, Stadler H, Woltering T, Mutel V (1998) In vitro binding characteristics of a new selective group II metabotropic glutamate receptor radioligand, [3H]LY354740, in rat brain. Mol Pharmacol 53:228–233
Schoepp DD, Conn PJ (1993) Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol Sci 14:13–20
Schoepp DD, Jane DE, Monn JA (1999) Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38:1431–1476
Skerry TM, Genever PG (2001) Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 22:174–181
Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S (1992) A family of metabotropic glutamate receptors. Neuron 8:169–179
Tanabe Y, Nomura A, Masu M, Shigemoto R, Mizuno N, Nakanishi S (1993) Signal transduction, pharmacological properties, and expression pattern of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci 13:1372–1378
Thomsen C, Dalby NO (1998) Roles of metabotropic glutamate receptor subtypes in modulation of pentylenetetrazole-induced seizure activity in mice. Neuropharmacology 37:1465–1473
Thomsen C, Mulvihill ER, Haldeman B, Pickering DS, Hampson DR, Suzdak PD (1993) A pharmacological characterization of the mGluR1α subtype of the metabotropic glutamate receptor expressed in a cloned baby hamster kidney cell line. Brain Res 619:22
Thomsen C, Boel E, Suzdak PD (1994) Action of phenylglycine analogs at subtypes of the metabotropic glutamate receptor family. Eur J Pharmacol 267:77–84
Thomsen C, Bruno V, Nicoletti F, Marinozzi M, Pelliciari R (1996) (2S,1′S,2′S,3′R)-2-(2′-carboxy-3′-phenylcyclopropyl)glycine, a potent and selective antagonist of type 2 metabotropic glutamate receptors. Mol Pharmacol 50:6–9
Varney MA, Suto CM (2000) Discovery of subtype-selective metabotropic glutamate receptor ligands using functional HTS assays. Drug Discov Today HTS Suppl 1:20–26
Watkins J, Collingridge G (1994) Phenylglycine derivatives as antagonists of metabotropic glutamate receptors. Trends Pharmacol Sci 15:333–342
Excitatory Amino Acid Transporters
Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 14:5559–5569
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Robinson MB, Sinor JD, Dowd LA, Kerwin JF Jr (1993) Subtypes of sodium-dependent high-affinity l-[3H]glutamate transport activity. Pharmacologic specificity and regulation by sodium and potassium. J Neurochem 60:167–179
Seal RP, Amara SG (1999) Excitatory amino acid transporters: a family in flux. Annu Rev Pharmacol Toxicol 39:431–456
Vandenberg RJ (1998) Molecular pharmacology and physiology of glutamate transporters in the central nervous system. Clin Exp Pharmacol Physiol 25:393–400
Vandenberg RJ, Arriza JL, Amara SG, Kavanaugh MP (1995) Constitutive ion fluxes and substrate binding domains of human glutamate transporters. J Biol Chem 270:17668–17671
Vandenberg RJ, Mitrovic AD, Chebib M, Balcar VJ, Johnston GAR (1997) Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol Pharmacol 51:809–815
Woodhull AM (1973) Ion blockage of sodium channels in nerve. J Gen Physiol 61:667–708
[35S]TBPS Binding in Rat Cortical Homogenates and Sections
Casida JE, Palmer CJ, Cole LM (1985) Bicycloorthocarboxylate convulsants. Potent GABAA receptor antagonists. Mol Pharmacol 28:246–253
Gee KW, Lawrence LJ, Yamamura HI (1986) Modulation of the chloride ionophore by benzodiazepine receptor ligands: influence of gamma-aminobutyric acid and ligand efficacy. Mol Pharmacol 30:218–225
Macksay G, Ticku MK (1985a) Dissociation of [35S]-t-butylbicyclophosphorothionate binding differentiates convulsant and depressant drugs that modulate GABAergic transmission. J Neurochem 44:480–486
Macksay G, Ticku MK (1985b) GABA, depressants and chloride ions affect the rate of dissociation of [35S]-t-butyl-bicyclophosphorothionate binding. Life Sci 37:2173–2180
Olsen RW, Yang J, King RG, Dilber A, Stauber GB, Ransom RW (1986) Barbiturate and benzodiazepine modulation of GABA receptor binding and function. Life Sci 39:1969–1976
Squires RF, Casida JE, Richardson M, Saederup E (1983) [35S]t-Butylbicyclophosphorothionate binds with high affinity to brain specific sites coupled to γ-aminobutyric acid-A and ion recognition sites. Mol Pharmacol 23:326–336
Supavilai P, Karabath M (1984) [35S]-t-Butylbicyclophosphorothionate binding sites are constituents of the γ-aminobutyric acid benzodiazepine receptor complex. J Neurosci 4:1193–1200
Trifiletti RR, Snowman AM, Snyder SH (1984) Anxiolytic cyclopyrrolone drugs allosterically modulate the binding of [35S]t-butylbicyclophosphorothionate to the benzodiazepine/γ-aminobutyric acid-A receptor/chloride anionophore complex. Mol Pharmacol 26:470–476
Trifiletti RR, Snowman AM, Snyder SH (1985) Barbiturate recognition site on the GABA/Benzodiazepine receptor complex is distinct from the picrotoxin/TBPS recognition site. Eur J Pharmacol 106:441–447
[3H]glycine Binding in Rat Cerebral Cortex
Baron BM, Harrison BL, Miller FP, McDonald IA, Salituro FG, Schmidt CJ, Sorensen SM, White HS, Palfreyman MG (1990) Activity of 5,7-dichlorokynurenic acid, a potent antagonist at the N-methyl-d-aspartate receptor-associated glycine binding site. Mol Pharmacol 38:554–561
Baron BM, Siegel BW, Harrison BL, Gross RS, Hawes C, Towers P (1996) [3H]MDL 105,519, a high affinity radioligand for the N-methyl-d-aspartate receptor-associated glycine recognition site. J Pharmacol Exp Ther 279:62–68
Becker L, von Wegener J, Schenkel J, Zeilhofer HU, Swandulla D, Weiher H (2002) Disease specific human glycine receptor αl subunit causes hyperekplexia phenotype and impaired glycine and GABAA-receptor transmission in transgenic mice. J Neurosci 22:2505–2512
Bonhaus DW, Burge BC, McNamara JO (1978) Biochemical evidence that glycine allosterically regulates an NMDA receptor-coupled ion channel. Eur J Pharmacol 142:489–490
Bonhaus DW, Yeh G-C, Skaryak L, McNamara JO (1989) Glycine regulation of the N-methyl-d-aspartate receptorgated ion channel in hippocampal membranes. Mol Pharmacol 36:273–279
Chazot PL, Reiss C, Chopra B, Stephenson FA (1998) [3H]MDL 105,519 binds with equal high affinity to both assembled and unassembled NR1 subunits of the NMDA receptor. Eur J Pharmacol 353:137–140
Cotman CW, Monaghan DT, Ottersen OP, Storm-Mathisen J (1987) Anatomical organization of excitatory amino acid receptors and their pathways. Trends Neurosci 10:273–280
Danysz W, Wroblewski JT, Brooker G, Costa E (1989) Modulation of glutamate receptors by phencyclidine and glycine in the rat cerebellum: cGMP increase in vivo. Brain Res 479:270–276
Foster AC, Kemp JA, Leeson PD, Grimwood S, Donald AE, Marshall GR, Priestley T, Smith JD, Carling RW (1992) Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-d-aspartate receptor from rat brain. Mol Pharmacol 41:914–922
Hargreaves RJ, Rigby M, Smith D, Hill RG (1993) Lack of effect of L-687,414 ((+)-cis-4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology. Br J Pharmacol 110:36–42
Hofner G, Wanner KT (1997) Characterization of the binding of [3H]MDL 105,519, a radiolabelled antagonist for the N-methyl-d-aspartate receptor-associated glycine site to pig cortical brain membranes. Neurosci Lett 226:79–82
Jansen KLR, Dragunow M, Faull RLM (1989) [3H]Glycine binding sites, NMDA and PCP receptors have similar distributions in the human hippocampus: an autoradiographic study. Brain Res 482:174–1178
Kessler M, Terramani T, Lynch B, Baudry M (1989) A glycine site associated with N-methyl-d-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem 52:1319–1328
Laube B, Maksay G, Schemm R, Betz H (2002) Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses? Trends Pharmacol Sci 23:519–527
Lynch JW (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84:1051–1095
Monahan JB, Corpus VM, Hood WF, Thomas JW, Compton RP (1989) Characterization of a [3H]glycine recognition site as a modulatory site of the N-Methyl-d-aspartate receptor complex. J Neurochem 53:370–375
Oliver MW, Kessler M, Larson J, Schottler F, Lynch G (1990) Glycine site associated with the NMDA receptor modulates long-term potentiation. Synapse 5:265–270
Ransom RW, Deschenes NL (1988) NMDA-induced hippocampal [3H]norepinephrine release is modulated by glycine. Eur J Pharmacol 156:149–155
Rao TS, Cler JA, Emmet MR, Mick SJ, Iyengar S, Wood PL (1990) Glycine, glycinamide, and d-serine act as positive modulators of signal transduction at the N-methyl-d-aspartate (NMDA) receptor in vivo: differential effects on mouse cerebellar cyclic guanosine monophosphate levels. Neuropharmacology 29:1075–1080
Rees MI, Lewis TM, Kwok JBJ, Mortier GR, Govaert P, Snell RG, Schofield PR, Owen MJ (2002) Hyperekplexia associated with compound heterozygote mutations in the β-subunit of the human inhibitory glycine receptor. (GLRB). Hum Mol Genet 11:853–860
Reynolds IJ, Murphy SN, Miller RJ (1987)3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine. Proc Natl Acad Sci U S A 84:7744–7748
Sacaan AI, Johnson KM (1989) Spermine enhances binding to the glycine site associated with N-methyl-d-aspartate receptor complex. Mol Pharmacol 36:836–839
Schmieden V, Betz H (1995) Pharmacology of the inhibitory glycine receptor: agonist and antagonist actions of amino acids and piperidine carboxylic compounds. Mol Pharmacol 48:919–927
Snell LD, Morter RS, Johnson KM (1987) Glycine potentiates N-methyl-d-aspartate induced [3H]TCP binding to rat cortical membranes. Neurosci Lett 83:313–317
Snell LD, Morter RS, Johnson KM (1988) Structural requirements for activation of the glycine receptor that modulates the N-methyl-d-aspartate operated ion channel. Eur J Pharmacol 156:105–110
Thomson AM (1989) Glycine modulation of the NMDA receptor/channel complex. Trends Neurosci 12:349–353
White HS, Harmsworth WL, Sofia RD, Wof HH (1995) Felbamate modulates the strychnine-insensitive glycine receptor. Epilepsy Res 20:41–48
[3H]strychnine-Sensitive Glycine Receptor
Betz H, Kuhse J, Schmieden V, Laube B, Harvey R (1998) Structure, diversity and pathology of the inhibitory glycine receptor. Naunyn-Schmiedeberg’s Arch Pharmacol 358(Suppl 2):R 570
Braestrup C, Nielsen M, Krogsgaard-Larsen P (1986) Glycine antagonists structurally related to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol inhibit binding of [3H]strychnine to rat brain membranes. J Neurochem 47:691–696
Bristow DR, Bowery NG, Woodruff GN (1986) Light microscopic autoradiographic localisation of [3H]glycine and [3H]strychnine binding sites in rat brain. Eur J Pharmacol 126:303–307
Bruns RF, Welbaum BEA (1985) A sodium chloride shift method to distinguish glycine agonists from antagonists in [3H]strychnine binding. Fed Proc 44:1828
Graham D, Pfeiffer F, Simler R, Betz H (1985) Purification and characterization of the glycine receptor of pig spinal cord. Biochemistry 24:990–994
Johnson G, Nickell DG, Ortwine D, Drummond JT, Bruns RF, Welbaum BE (1989) Evaluation and synthesis of aminohydroxyisoxazoles and pyrazoles as potential glycine agonists. J Med Chem 32:2116–2128
Johnson G, Drummond JT, Boxer PA, Bruns RF (1992) Proline analogues as agonists at the strychnine-sensitive glycine receptor. J Med Chem 35:233–241
Kishimoto H, Simon JR, Aprison MH (1981) Determination of the equilibrium constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system. J Neurochem 37:1015–1024
Lambert DM, Poupaert JH, Maloteaux JM, Dumont P (1994) Anticonvulsant activities of N-benzyloxycarbonylglycine after parenteral administration. NeuroReport 5:777–780
Marvizon JCG, Vázquez J, Calvo MG, Mayor F Jr, Gómez AR, Valdivieso F, Benavides J (1986) The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites. Mol Pharmacol 30:590–597
Saitoh T, Ishida M, Maruyama M, Shinozaki H (1994) A novel antagonist, phenylbenzene-ω-phosphono-a-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord. Br J Pharmacol 113:165–170
Schmieden V, Jezequel S, Beth H (1996) Novel antagonists of the inhibitory glycine receptor derived from quinolinic acid compounds. Mol Pharmacol 48:919–927
Simmonds MA, Turner JP (1985) Antagonism of inhibitory amino acids by the steroid derivative RU5135. Br J Pharmacol 84:631–635
Young AB, Snyder SH (1974) Strychnine binding in rat spinal cord membranes associated with the synaptic glycine receptor: co-operativity of glycine interactions. Mol Pharmacol 10:790–809
Electrical Recordings from Hippocampal Slices in Vitro
Alger BE (1984) Hippocampus. Electrophysiological studies of epileptiform activity in vitro. In: Dingledine R (ed) Brain slices. Plenum Press, New York/London, pp 155–199
Alger BE, Nicoll RA (1982) Pharmacological evidence of two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol 328:125–141
Alger BE, Dhanjal SS, Dingledine R, Garthwaite J, Henderson G, King GL, Lipton P, North A, Schwartzkroin PA, Sears TA, Segal M, Whittingham TS, Williams J (1984) Brain slice methods. In: Dingledine R (ed) Brain slices. Plenum Press, New York/London, pp 381–437
Bernard C, Wheal HV (1995) Plasticity of AMP and NMDA receptor mediated epileptiform activity in a chronic model of temporal lobe epilepsy. Epilepsy Res 21:95–107
Bingmann D, Speckmann EJ (1986) Actions of pentylenetetrazol (PTZ) on CA3 neurons in hippocampal slices of guinea pigs. Exp Brain Res 64:94–104
Blanton MG, Turco JJL, Kriegstein AR (1989) Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods 30:203–210
Coan EJ, Saywood W, Collingridge GL (1987) MK-801 blocks NMDA receptor-mediated synaptic transmission and long term potentiation in rat hippocampal slices. Neurosci Lett 80:111–114
Crain SM (1972) Tissue culture models of epileptiform activity. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 291–316
Dingledine R, Dodd J, Kelly JS (1980) The in vitro brain slice as a useful neurophysiological preparation for intracellular recording. J Neurosci Methods 2:323–362
Fisher RS (1987) The hippocampal slice. Am J EEG Technol 27:1–14
Fisher RS, Alger BE (1984) Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J Neurosci 4:1312–1323
Fredholm BB, Dunwiddie TV, Bergman B, Lindström K (1984) Levels of adenosine and adenine nucleotides in slices of rat hippocampus. Brain Res 295:127–136
Gahwiler BH (1988) Organotypic cultures of neuronal tissue. Trends Neurol Sci 11:484–490
Harrison NL, Simmonds MA (1985) Quantitative studies on some antagonists of N-methyl-d-aspartate in slices of rat cerebral cortex. Br J Pharmacol 84:381–391
Langmoe IA, Andersen P (1981) The hippocampal slice in vitro. A description of the technique and some examples of the opportunities it offers. In: Kerkut GA, Wheal HV (eds) Electrophysiology of isolated mammalian CNS preparations. Academic, London/New York, pp 51–105
Liu FC, Takahashi H, Mc Kay RDG, Graybiel AM (1995) Dopaminergic regulation of transcription factor expression in organotypic cultures of developing striatum. J Neurosci 15:2367–2384
Misgeld U (1992) Hippocampal slices. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 41–44
Mosfeldt Laursen A (1984) The contribution of in vitro studies to the understanding of epilepsy. Acta Neurol Scand 69:367–375
Müller CM (1992) Extra- and intracellular voltage recording in the slice. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 249–295
Oh DJ, Dichter MA (1994) Effect of a γ-aminobutyric acid uptake inhibitor, NNC-711, on spontaneous postsynaptic currents in cultured rat hippocampal neurons: implications for antiepileptic drug development. Epilepsia 35:426–430
Okada Y, Ozawa S (1980) Inhibitory action of adenosine on synaptic transmission in the hippocampus of the guinea pig in vitro. Eur J Pharmacol 68:483–492
Oliver AP, Hoffer BJ, Wyatt RJ (1977) The hippocampal slice: a model system for studying the pharmacology of seizures and for screening of anticonvulsant drugs. Epilepsia 18:543–548
Pandanaboina MM, Sastry BR (1984) Rat neocortical slice preparation for electrophysiological and pharmacological studies. J Pharmacol Methods 11:177–186
Saltarelli MD, Lowenstein PR, Coyle JT (1987) Rapid in vitro modulation of [3H]hemicholinium-3 binding sites in rat striatal slices. Eur J Pharmacol 135:35–40
Schlicker E, Fink K, Zentner J, Göthert M (1996) Presynaptic inhibitory serotonin autoreceptors in the human hippocampus. Naunyn-Schmiedeberg’s Arch Pharmacol 354:393–396
Schwartzkroin PA (1975) Characteristics of CA1 neurons recorded intracellularly in the hippocampal in vitro slice preparation. Brain Res 85:423–436
Siggins GR, Schubert P (1981) Adenosine depression of hippocampal neurons in vitro: an intracellular study of dose-dependent actions on synaptic and membrane potentials. Neurosci Lett 23:55–60
Skrede KK, Westgard RH (1971) The transverse hippocampal slice: a well-defined cortical structure maintained in vitro. Brain Res 35:589–659
Stoppini L, Buchs PA, Muller D (1991) A simple method for oganotypic cultures of nervous tissue. J Neurosci Methods 37:173–182
Stuart GJ, Dodt HU, Sakmann B (1993) Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch 423:511–518
Teyler TT (1980) Brain slice preparation: hippocampus. Brain Res Bull 5:391–403
Electrical Recordings from Isolated Nerve Cells
Banker GA, Cowan WM (1977) Rat hippocampal neurons in dispersed cell culture. Brain Res 126:397–425
Caulfield MP, Brown DA (1992) Cannabinoid receptor agonists inhibit Ca current in NG108–15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 106:231–232
Chen Q-X, Stelzer A, Kay AR, Wong RKS (1990) GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea-pig hippocampal neurones. J Physiol 420:207–221
Delmas P, Brown DA, Dayrell M, Abogadie FC, Caulfield MP, Buckley NJ (1998) On the role of endogenous G-protein β γ subunits in N-type Ca2+ current inhibition by neurotransmitters in rat sympathetic neurones. J Physiol 506:319–329
Gola M, Niel JP (1993) Electrical and integrative properties of rabbit sympathetic neurons re-evaluated by patch-clamping non-dissociated cells. J Physiol 460:327–349
Gola M, Niel JP, Bessone R, Fayolle R (1992) Single channel and whole cell recordings from non dissociated sympathetic neurones in rabbit coeliac ganglia. J Neurosci Methods 43:13–22
Gonzales F, Farbman AI, Gesteland RC (1985) Cell and explant culture of olfactory chemoreceptor cells. J Neurosci Methods 14:77–90
Jirikowski G, Reisert I, Pilgrim C (1981) Neuropeptides in dissociated cultures of hypothalamus and septum; quantification of immunoreactive neurons. Neuroscience 6:1953–1960
Kay AR, Wong RKS (1986) Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems. J Neurosci Methods 16:227–238
McGivern JG, Patmore L, Sheridan RD (1995) Actions of the novel neuroprotective agent, lifarizine (RS-87476), on voltage- dependent sodium currents in the neuroblastoma cell line, NIE-115. Br J Pharmacol 114:1738–1744
McLarnon JG (1991) The recording of action potential currents as an assessment for drug actions on excitable cells. J Pharmacol Methods 26:105–111
McLarnon JG, Curry K (1990) Single channel properties of the N-methyl-d-aspartate receptor channel using NMDA and NMDA agonists: on-cell recordings. Exp Brain Res 82:82–88
Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:799–802
Sakmann B, Neher E (1983) Single channel recording. Plenum Press, New York
Smith PA (1995) Methods for studying neurotransmitter transduction mechanisms. J Pharmacol Toxicol Methods 33:63–73
Stolc S (1994) Pyridoindole stobadine is a nonselective inhibitor of voltage-operated ion channels in rat sensory neurons. Gen Physiol Biophys 13:259–266
Isolated Neonatal Rat Spinal Cord
Akagi H, Konishi S, Otsuka M, Yanagisawa M (1985) The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord. Br J Pharmacol 84:663–673
Bleakman D, Rusin KI, Chard PS, Glaum SR, Miller RJ (1992) Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn. Mol Pharmacol 42:192–196
Boxall SJ, Thompson SWN, Dray A, Dickenson AH, Urban L (1996) Metabotropic glutamate receptor activation contribute to nociceptive reflex activity in the rat spinal cord in vitro. Neuroscience 74:13–20
Dong X-W, Morin D, Feldman JL (1996) Multiple actions of 1S, 3R-ACPD in modulating endogenous synaptic transmission to spinal respiratory motoneurons. J Neurosci 16:4971–4982
Evans RH, Francis AA, Jones AW, Smith DAS, Watkins JC (1982) The effects of a series of ω-phosphonic α-carboxylic amino acids on electrically evoked and excitant amino-acid-induced responses in isolated spinal cord preparations. Br J Pharmacol 75:65–75
Faber ESL, Chambers JP, Brugger F, Evans RH (1997) Depression of A and C fibre-evoked segmental reflexes by morphine and clonidine in the in vitro spinal cord of the neonatal rat. Br J Pharmacol 120:1390–1396
Guo JZ, Yoshioka K, Otsuka M (1998) Effects of a tachykinin NK3 receptor antagonist, SR 142801, studied in isolated neonatal spinal cord. Neuropeptides 32:537–542
Ishida M, Shinozakai H (1991) Novel kainate derivatives: potent depolarizing actions on spinal motoneurons and dorsal root fibres in newborn rats. Br J Pharmacol 104:873–878
Ishida M, Akagi H, Shimamoto K, Ohfune Y, Shinozaki H (1990) A potent metabotropic glutamate receptor agonist: electrophysiological actions of a conformationally restricted glutamate analogue in the rat spinal cord and Xenopus oocytes. Brain Res 537:311–314
Ishida M, Saitoh T, Shimamoto K, Ohfune Y, Shinozaki H (1993) A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord. Br J Pharmacol 109:1169–1177
Jane DE, Jones PLSJ, Pook PCK, Tse HW, Watkins JC (1994) Actions of two new antagonists showing selectivity for different subtypes of metabotropic glutamate receptor in the neonatal rat spinal cord. Br J Pharmacol 112:809–816
Kendig JJ, Savola MKT, Woodley SJ, Maze M (1991) α 2-adrenoceptors inhibit a nociceptive response in neonatal rat spinal cord. Eur J Pharmacol 192:293–300
King AE, Lopez-Garcia JA, Cumberbatch M (1992) Antagonism of synaptic potentials in ventral horn neurons by 6-cyano-7-nitroquninoxaline-2,3-dione: a study in the rat spinal cord in vitro. Br J Pharmacol 107:375–381
Lev-Tov A, Pinco M (1992) In vitro studies of prolonged synaptic depression in the neonatal rat spinal cord. J Physiol 447:149–169
Nussbaumer JC, Yanagisawa M, Otsuka M (1989) Pharmacologic properties of a C fibre response evoked by saphenous nerve stimulation in an isolated spinal cord-nerve preparation of the newborn rat. Br J Pharmacol 98:373–382
Ohno Y, Warnick JE (1988) Effects of thyrotropin-releasing hormone on phencyclidine- and ketamine-induced spinal depression in neonatal rats. Neuropharmacology 27:1013–1018
Ohno Y, Warnick JE (1990) Selective depression of the segmental polysynaptic reflex by phencyclidine and its analogs in the rat in vitro: Interaction with N-methyl-d-aspartate receptors. J Pharmacol Exp Ther 252:246–252
Otsuka M, Konishi S (1974) Electrophysiology of mammalian spinal cord in vitro. Nature 252:733–734
Otsuka M, Yanagisawa M (1988) Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord tail preparation of the newborn rat. J Physiol 395:255–270
Pook P, Brugger F, Hawkins NS, Clark KC, Watkins JC, Evans RH (1993) A comparison of action of agonists and antagonists at non-NMDA receptors of C fibres and motoneurons of the immature rat spinal cord in vitro. Br J Pharmacol 108:179–184
Shinozaki H, Ishida M, Shimamoto K, Ohfune Y (1989) Potent NMDA-like actions and potentiation of glutamate responses by conformational variants of a glutamate analogue in the rat spinal cord. Br J Pharmacol 98:1213–1224
Smith JC, Feldman JL (1987) In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion. J Neurosci Methods 21:321–333
Thompson SWN, Gerber G, Sivilotti LG, Woolf CJ (1992) Long duration of ventral root potentials in the neonatal spinal cord in vitro: the effects of ionotropic and metabotropic excitatory amino acid receptor antagonists. Brain Res 595:87–97
Woodley SJ, Kendig JJ (1991) Substance P and NMDA receptors mediate a slow nociceptive ventral root potential in neonatal rat spinal cord. Brain Res 559:17–22
Yanagisawa M, Otsuka M, Konishi S, Akagi H, Folkers K, Rosell S (1982) A substance P antagonist inhibits a slow reflex response in the spinal cord of the newborn rat. Acta Physiol Scand 116:109–112
Yanagisawa MT, Murakoshi T, Tamai S, Otsuka M (1985) Tailpinch method in vitro and the effect of some antinociceptive compounds. Eur J Pharmacol 106:231–239
Zeman S, Lodge D (1992) Pharmacological characterization of non-NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro. Br J Pharmacol 106:367–372
Cell Culture of Neurons
Araujo DM, Cotman CW (1993) Trophic effects of interleukin-4, -7, and -8 on hippocampal neuronal cultures: potential involvement of glial-derived factors. Brain Res 600:49–55
Banker GA, Cowan WM (1977) Rat hippocampal neurons in dispersed cell culture. Brain Res 126:397–425
Brewer GJ (1997) Isolation and culture of adult hippocampal neurons. J Neurosci Methods 71:143–155
Brewer GJ (1999) Regeneration and proliferation of embryonic and adult rat hippocampal neurons in culture. Exp Neurol 159:237–247
Brewer GJ, Deshmane S, Ponnusamy E (1998) Precocious axons and improved survival of rat hippocampal neurons on lysine-alanine polymer substrate. J Neurosci Methods 85:13–20
Canals S, Casarejos MJ, Rodríguez-Martin E, de Bernardo S, Mena MA (2001) Neurotrophic and neurotoxic effects of nitric oxide on fetal midbrain cultures. J Neurochem 76:56–68
Chaudieu I, Privat A (1999) Neuroprotection of cultured foetal rat hippocampal cells against glucose deprivation: are GABAergic neurons less vulnerable or more sensitive to TCP protection? Eur J Neurosci 11:2413–2421
Ehret A, Haaf A, Jeltsch H, Heinrich B, Feuerstein TJ, Jakisch R (2001) Modulation of electrically evoked acetylcholine release in cultured septal neurones. J Neurochem 76:555–564
Flavin MP, Ho LT (1999) Propentofylline protects neurons in culture from death triggered by macrophage or microglia secretory products. J Neurosci Res 56:54–59
Hampson RE, Mu J, Deadwyler SA (2000) Cannabinoid and kappa opioid receptors reduced potassium K current via activation of Gs proteins in cultured hippocampal neurons. J Neurophysiol 84:2356–2364
Jirikowski G, Reisert I, Pilgrim Ch (1981) Neuropeptides in dissociated cultures of hypothalamus and septum: quantitation of immunoreactive neurons. Neuroscience 6:1953–1960
Li YX, Zhang Y, Lester HA, Schuman EM, Davidson N (1998) Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons. J Neurosci 18:10231–10240
López E, Arce C, Vicente S, Oset-Gasque MJ, González MP (2001) Nicotinic receptors mediate the release of amino acid neurotransmitters in cultured cortical neurons. Cereb Cortex 11:158–163
May PC, Robison PM, Fuson KS (1999) Stereoselective neuroprotection by a novel 2,3-benzodiazepine non-competitive AMPA antagonist against non-NMDA receptor mediated excitotoxicity in primary rat hippocampal culture. Neurosci Lett 262:219–221
Mitoma J, Ito M, Furuya S, Hirabayashi Y (1998) Bipotential roles of ceramide in the growth of hippocampal neurones: promotion of cell survival and dendritic outgrowth in dose and developmental stage-dependent manners. J Neurosci Res 51:712–722
Noh K-M, Koh J-Y (2000) Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. J Neurosci 20:RC111, 1–5
Novitskaya V, Grigorian M, Kriajevska M, Tarabykina S, Bronstein I, Berezin V, Bock E, Lukanidin E (2000) Oligomeric forms of the metastasis-related Mts1 (S100A4) protein stimulate neuronal differentiation in cultures of rat hippocampal neurons. J Biol Chem 275:41278–41286
Pickard L, Noël J, Henley JM, Collingridge GL, Molnar E (2000) Developmental changes in synaptic AMPA and NMDA receptor distribution and AMPA receptor subunit composition in living hippocampal neurons. J Neurosci 20:7922–7931
Saluja I, Granneman JG, Skoff RP (2001) PPAR δ agonists stimulate oligodendrocyte differentiation in tissue culture. Glia 33:191–204
Semkowa I, Wolz P, Krieglstein J (1998) Neuroprotective effect of 5-HT1A receptor agonist, Bay X 3702, demonstrated in vitro and in vivo. Eur J Pharmacol 359:251–260
Semkowa I, Häberlein C, Krieglstein J (1999) Ciliary neurotrophic factor protects hippocampal neurons from excitotoxic damage. Neurochem Int 35:1–10
Sinor JD, Du S, Venneti S, Blitzblau RC, Leszkiewicz DN, Rosenberg PA, Aizenman E (2000) NMDA and glutamate evoke excitotoxicity at distinct cellular locations in rat cortical neurones in vitro. J Neurosci 20:8831–8837
Skaper SD, Facci L, Milani L, Leon A, Toffano G (1990) Culture and use of primary and clonal neural cells. In: Conn PM (ed) Methods in neuroscience, vol 2. Academic, San Diego, pp 17–33
Skaper SD, Leon A, Facci L (1993) Basic fibroblast growth factor modulates sensitivity of cultured hippocampal pyramidal neurones to glutamate cytotoxicity: interaction with ganglioside GM1. Brain Res Dev Brain Res 71:1–8
Skaper SD, Facci L, Kee WJ, Strijbös PJLM (2001) Potentiation by histamine of synaptically mediated excitotoxicity in cultured hippocampal neurones: a possible role for mast cells. J Neurochem 76:47–55
Tang DG, Tokumoto YM, Apperly JA, Lloyd AC, Raff MC (2001) Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Science 291:868–871
Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 97:14720–14725
Vergun O, Sobolevsky AI, Yelshansky MV, Keelan J, Khodorov BI, Duchen MR (2001) Exploration of the role of reactive oxygen species in glutamate neurotoxicity in rat hippocampal neurons in culture. J Physiol 531:147–163
Yamagishi S, Yamada M, Ishikawa Y, Matsumoto T, Ikeuchi T, Hatanaka H (2001) p38 Mitogen-activated protein kinase regulates low potassium-induced c-Jun phosphorylation and apoptosis in cultured cerebellar granule neurons. J Biol Chem 276:5129–5133
Electroshock in Mice
Cashin CH, Jackson H (1962) An apparatus for testing anticonvulsant drugs by electroshock seizures in mice. J Pharm Pharmacol 14:445–475
Kitano Y, Usui C, Takasuna K, Hirohashi M, Nomura M (1996) Increasing-current electroshock seizure test: a new method for assessment of anti- and pro-convulsant activities of drugs in mice. J Pharmacol Toxicol Methods 35:25–29
Löscher W, Stephens DN (1988) Chronic treatment with diazepam or the inverse benzodiazepine receptor agonist FG 7142 causes different changes in the effects of GABA receptor stimulation. Epilepsy Res 2:253–259
Rastogi SA, Ticku MK (1985) Involvement of a GABAergic mechanism in the anticonvulsant effect of phenobarbital against maximal electroshock-induced seizures in rats. Pharmacol Biochem Behav 222:141–146
Sohn YJ, Levitt B, Raines A (1970) Anticonvulsive properties of diphenylthiohydantoin. Arch Int Pharmacodyn 188:284–289
Swinyard EA (1972) Electrically induced convulsions. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 433–458
Swinyard EA, Brown WC, Goodman LS (1952) Comparative assays of antiepileptic drugs in mice and rats. J Pharmacol Exp Ther 106:319–330
Toman JEP (1964) Animal techniques for evaluating anticonvulsants. In: Nodin JH, Siegler PE (eds) Animal and clinical techniques in drug evaluation, vol 1. Year Book Medical Publishers, Chicago, pp 348–352
Toman JEP, Everett GM (1964) Anticonvulsants. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities: pharmacometrics. Academic, London, New York, pp 287–300
Turner RA (1965) Anticonvulsants. Academic, New York/London, pp 164–172
Woodbury LA, Davenport VO (1952) Design and use of a new electroshock seizure apparatus and analysis of factors altering seizure threshold and pattern. Arch Int Pharmacodyn 92:97–107
Isoniazid-Induced Convulsions in Mice
Hahn F, Oberdorf A (1960) Vergleichende Untersuchungen über die Krampfwirkung von Begrimid, Pentetrazol und Pikrotoxin. Arch Int Pharmacodyn 135:9–30
Leander JD, Lawson RR, Ornstein PL, Zimmerman DM (1988) N-methyl-d-aspartic acid induced lethality in mice: selective antagonism by phencyclidine-like drugs. Brain Res 448:115–120
Pollack GM, Shen DD (1985) A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in the rat. J Pharmacol Methods 13:135–146
Shouse MN, Siegel JM, Wu MF, Szymusiak R, Morrison AR (1989) Mechanism of seizure suppression during rapid-eye-movement (REM) sleep in cats. Brain Res 505:271–282
Snead OC III (1988) γ-Hydroxybutyrate model of generalized absence seizures: further characterization and comparison with other absence models. Epilepsia 29:361–368
Stone WE (1972) Systemic chemical convulsants and metabolic derangements. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 407–432
Testa R, Graziani L, Graziani G (1983) Do different anticonvulsant tests provide the same information concerning the profiles of antiepileptic activity? Pharmacol Res Commun 15:765–774
Toussi HR, Schatz RAS, Waszczak BL (1987) Suppression of methionine sulfoximine seizures by intranigral γ -vinyl GABA injection. Eur J Pharmacol 137:261–264
Tursky WA, Cavalheiro EA, Coimbra C, da Penha Berzaghi M, Ikonomidou-Turski C, Turski L (1987) Only certain antiepileptic drugs prevent seizures induced by pilocarpine. Brain Res Rev 12:281–305
Bicuculline Test in Rats
Buckett WR (1981) Intravenous bicuculline test in mice: characterisation with GABAergic drugs. J Pharmacol Methods 5:35–41
Clineschmidt BV, Martin GE, Bunting PR (1982) Anticonvulsant activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res 2:123–134
Czuczwar SJ, Frey HH, Löscher W (1985) Antagonism of N-methyl-d, l-aspartic acid-induced convulsions by antiepileptic drugs and other agents. Eur J Pharmacol 108:273–280
Lloyd KG, Morselli PL (1987) Psychopharmacology of GABAergic drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York pp 183–195
Mecarelli O, de Feo MR, Rina MF, Ricci GF (1988) Effects of progabide on bicuculline-induced epileptic seizures in developing rats. Clin Neuropharmacol 11:443–453
4-Aminopyridine-Induced Seizures in Mice
Morales-Villagran A, Urena-Guerrero ME, Tapia R (1996) Protection by NMDA receptor antagonists against seizures induced by intracerebral administration of 4-aminopyridine. Eur J Pharmacol 305:87–93
Rogawski MA, Porter RJ (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev 42:223–286
Rutecki PA, Lebeda FJ, Johnston D (1987) 4-aminopyridine produces epileptiform activity in hippocampus and enhances synaptic excitation and inhibition. J Neurophysiol 57:1911–1924
Schaefer EW Jr, Brunton RB, Cunningham DJ (1973) A summary of the acute toxicity of 4-aminopyridine to birds and mammals. Toxicol Appl Pharmacol 26:532–538
Yamaguchi SI, Rogawski MA (1992) Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice. Epilepsy Res 11:9–16
3-Nitropropionic Acid-Induced Seizures in Mice
Alston TA, Mela L, Bright HL (1977) 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proc Natl Acad Sci U S A 74:3767–3771
Ludolph AC, He F, Spencer PS, Hammerstad J, Sabri M (1991) 3-Nitropropionic acid – exogenous animal neurotoxin and possible human striatal toxin. Can J Neurol Sci 18:492–498
Urbańska EM, Blaszczak P, Saran T, Kleinrok Z, Turski WA (1998) Mitochondrial toxin 3-nitropropionic acid evokes seizures in mice. Eur J Pharmacol 359:55–58
Urbańska EM, Blaszczak P, Saran T, Kleinrok Z, Turski WA (1999) AMPA/kainate-related mechanisms contribute to convulsant and proconvulsant effects of 3-nitropropionic acid. Eur J Pharmacol 370:251–256
Zuchora B, Wielosz M, Urbańska EM (2005) Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the model of 3-nitropropionic acid-induced seizures in mice. Eur Neuropsychopharmacol 15:85–93
Epilepsy Induced by Focal Lesions
Albe-Fessard D, Stutinsky F, Libouban S (1971) Atlas Stéréotaxique du Diencéphale du Rat Blanc. C.N.R.S., Paris
Anderer P, Barbanoj MJ, Saletu B, Semlitsch HV (1993) Restriction to a limited set of EEG-target variables may lead to misinterpretation of pharmaco-EEG results. Neuropsychobiology 27:112–116
Atsev E, Yosiphov T (1969) Changes in evoked perifocal electrical activity with an acute epileptogenic focus in cat’s cortex. Electroencephalogr Clin Neurophysiol 27:444
Bernhard CG, Bohm E (1955) The action of local anaesthetics on experimental epilepsy in cats and monkeys. Br J Pharmacol 10:288–295
Bernhard CG, Bohm E, Wiesel T (1956) On the evaluation of the anticonvulsive effect of local anaesthetics. Arch Int Pharmacodyn 108:392–407
Black RG, Abraham J, Ward AA Jr (1967) The preparation of tungstic acid gel and its use in the production of experimental epilepsy. Epilepsia 8:58–63
Blum B, Liban E (1960) Experimental basotemporal epilepsy in the cat. Discrete epileptogenic lesions produced in the hippocampus or amygdaloid by tungstic acid. Neurology 10:546–554
Campell AM, Holmes O (1984) Bicuculline epileptogenesis in the rat. Brain Res 323:239–246
Cavalheiro EA, Riche DA, Gal L, la Salle G (1982) Long-term effects of intrahippocampal kainic acid injections in rats: a method for inducing spontaneous recurrent seizures. Electroencephalogr Clin Neurophysiol 53:581–589
Daniels JC, Spehlman R (1973) The convulsant effect of topically applied atropine. Electroencephalogr Clin Neurophysiol 34:83–87
Dow RS, Fernández-Guardiola A, Manni E (1962) The production of cobalt experimental epilepsy in the rat. Electroencephalogr Clin Neurophysiol 14:399–407
Ferguson JH, Jasper HH (1971) Laminar DC studies of acetylcholine-activated epileptiform discharge in cerebral cortex. Electroencephalogr Clin Neurophysiol 30:377–390
Feria-Velasco A, Olivares N, Rivas F, Velasco M, Velasco F (1980) Alumina cream-induced focal motor epilepsy in cats. Arch Neurol 37:287–290
Fischer J, Holubar J, Malik V (1967) A new method of producing chronic epileptogenic cortical foci in the rat. Physiol Bohemoslov 16:272–277
Hanna GR, Stalmaster RM (1973) Cortical epileptic lesions produced by freezing. Neurology 23:918–925
Hawkins CA, Mellanby JH (1987) Limbic epilepsy induced by tetanus toxin: a longitudinal electroencephalographic study. Epilepsia 28:431–444
Karpiak SE, Graf L, Rapport MM (1976) Antiserum to brain gangliosides produces recurrent epileptiform activity. Science 194:735–737
Karpiak SE, Mahadik SP, Graf L, Rapport MM (1981) An immunological model of epilepsy: seizures induced by antibodies to GM1 ganglioside. Epilepsia 22:189–196
Kopeloff LM, Barrera SE, Kopeloff N (1942) Recurrent convulsive seizures in animals produced by immunologic and chemical means. Am J Psychiatry 98:881–902
Kopeloff L, Chusid JG, Kopeloff N (1955) Epilepsy in Maccaca mulatta after cortical or intracerebral alumina. Arch Neurol Psychiatry 74:523–526
Krupp E, Löscher W (1998) Anticonvulsant drug effects in the direct cortical ramp-stimulation model in rats: comparison with convulsive seizure models. J Pharmacol Exp Ther 285:1137–1149
Lange SC, Neafsey EJ, Wyler AR (1980) Neuronal activity in chronic ferric chloride epileptic foci in cats and monkey. Epilepsia 21:251–254
Loiseau H, Avaret N, Arrigoni E, Cohadon F (1987) The early phase of cryogenic lesions: an experimental model of seizures updated. Epilepsia 28:251–258
Marsan CA (1972) Focal electrical stimulation. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 147–172
Matsumoto H, Marsan CA (1964) Cortical cellular phenomena in experimental epilepsy: interictal manifestations. Exp Neurol 9:286–304
Mellanby J, Hawkins C, Mellanby H, Rawlins JNP, Impey ME (1984) Tetanus toxin as a tool for studying epilepsy. J Physiol Paris 79:207–215
Pei Y, Zhao D, Huang J, Cao L (1983) Zinc-induced seizures: a new experimental model of epilepsy. Epilepsia 24:169–176
Racine RJ (1972) Modification of seizure activity by electrical stimulation: I. After-discharge threshold. Electroencephalogr Clin Neurophysiol 32:269–279
Reid SA, Sypert GW, Boggs WM, Wilmore LJ (1979) Histopathology of the ferric-induced chronic epileptic focus in cat: a Golgi study. Exp Neurol 66:205–219
Remler MP, Marcussen WH (1986) Systemic focal epileptogenesis. Epilepsia 27:35–42
Remler MP, Sigvardt K, Marcussen WH (1986) Pharmacological response of systemically derived focal epileptic lesions. Epilepsia 27:671–6777
Stalmaster RM, Hanna GR (1972) Epileptic phenomena of cortical freezing in the cat: persistent multifocal effects of discrete superficial lesions. Epilepsia 13:313–324
Turski WA, Czuczwar SJ, Kleinrok Z, Turski L (1983) Cholinomimetics produce seizures and brain damage in rats. Experientia 39:1408–1411
Walton NY, Treiman DM (1989) Phenobarbital treatment of status epilepticus in a rodent model. Epilepsy Res 4:216–222
Walton NY, Gunnawan S, Treiman DM (1994) Treatment of experimental status epilepticus with the GABA uptake inhibitor, tiagabine. Epilepsy Res 19:237–244
Ward AA Jr (1972) Topical convulsant metals. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 13–35
Kindled Rat Seizure Model
Babington RG (1975) Antidepressives and the kindling effect. In: Fielding S, Lal H (eds) Antidepressants, vol 2, Industrial pharmacology. Futura Publishing Company, New York, pp 113–124
Croucher MJ, Cotterell KL, Bradford HF (1996) Characterization of N-methyl-d-aspartate (NMDA)-induced kindling. Biochem Soc Transact 24:295S
Durmuller N, Craggs M, Meldrum BS (1994) The effect of the non-NMDA receptor antagonists GYKI 52446 and NBQX and the competitive NMDA receptor antagonist D-CPPene on the development of amygdala kindling and on amygdala-kindled seizures. Epilepsy Res 17:167–174
Ebert U, Löscher W (1999) Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant epilepsy: influence of genetic factors. Epilepsy Res 33:217–226
Ebert U, Cramer S, Löscher W (1997) Phenytoin’s effect on the spread of seizures in the amygdala kindling model. Naunyn-Schmiedebergs Arch Pharmacol 356:341–347
Gal L, la Salle G (1981) Amygdaloid kindling in the rat: regional differences and general properties. In: Wada JA (ed) Kindling 2. Raven, New York, pp 31–47
Gilbert ME (1994) The phenomenology of limbic kindling. Toxicol Ind Health 10:4–5
Girgis M (1981) Kindling as a model for limbic epilepsy. Neuroscience 6:1695–1706
Goddard GV (1967) Development of epileptic seizures through brain stimulation at low intensity. Nature 214:1020–1021
Goddard GV, McIntyre DC, Leech CK (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25:295–330
Goddard GV, Dragunow M, Maru E, Macleod EK (1986) Kindling and the forces that oppose it. In: Doane BK, Livingston KE (eds) The limbic system: functional organization and clinical disorders. Raven, New York, pp 95–108
Heit MC, Schwark WS (1987) An efficient method for time course studies of antiepileptic drugs using the kindled rat seizure model. J Pharmacol Methods 18:319–325
Hoenack D, Loescher W (1989) Amygdala-kindling as a model for chronic efficacy studies on antiepileptic drugs: experiments with carbamazepine. Neuropharmacology 28:599–610
Koella WP (1985) Animal experimental methods in the study of antiepileptic drugs, Chapter 12. In: Frey HH, Danz D (eds) Antiepileptic drugs. Springer, Heidelberg/New York/Tokyo, pp 283–339
Löscher W (1998) Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy. Prog Neurobiol 54:721–741
Löscher W, Nolting B, Hönack D (1988) Evaluation of CPP, a selective NMDA antagonist, in various rodent models of epilepsy. Comparison with other NMDA antagonists, and with diazepam and phenobarbital. Eur J Pharmacol 152:9–17
Löscher W, Rundfeldt C, Honack D (1993) Pharmacological characterization of phenytoin-resistant amygdala-kindled rats, a new model of drug-resistant partial epilepsy. Epilepsy Res 15:207–219
Lothman EW, Salerno RA, Perlin JB, Kaiser DL (1988) Screening and characterization of anti-epileptic drugs with rapidly recurring hippocampal seizures in rats. Epilepsy Res 2:367–379
Mason CR, Cooper RM (1972) A permanent change in convulsive threshold in normal and brain-damaged rats with repeated small doses of pentylenetetrazol. Epilepsia 13:663–674
McNamara JO (1984) Kindling: an animal model of complex partial epilepsy. Ann Neurol 16(Suppl):S72–S76
McNamara JO (1986) Kindling model of epilepsy, Chapter 14. In: Delgado-Escueta AV, Ward AA, Woodbury DM, Porter RJ (eds) Basic mechanisms of the epilepsies. Molecular and cellular approaches, vol 44, Advances in neurology. Raven, New York, pp 303–318
Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotactic atlas of the brain, 2nd edn. Plenum Press, New York
Pinel JPJ, Rovner LI (1978) Experimental epileptogenesis: kindling-induced epilepsy in rats. Exp Neurol 58:190–202
Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr. Clin Neurophysiol 32:281–294
Racine R (1978) Kindling: the first decade. Neurosurgery 3:234–252
Schmidt J (1990) Comparative studies on the anticonvulsant effectiveness of nootropic drugs in kindled rats. Biomed Biochim Acta 49:413–419
Suzuki K, Mori N, Kittaka H, Iwata Y, Osonoe K, Niwa SI (1996) Anticonvulsant action of metabotropic glutamate receptor agonists in kindled amygdala of rats. Neurosci Lett 204:41–44
Wada JA (1977) Pharmacological prophylaxis in the kindling model of epilepsy. Arch Neurol 34:387–395
Wada JKA, Osawa T (1976) Spontaneous recurrent seizure state induced by daily amygdaloid stimulation in Senegalese baboons (Papio papio). Neurology 22:273–286
Wada JA, Mizoguichi T, Osawa T (1978) Secondarily generalized convulsive seizures induced by daily amygdaloid stimulation in rhesus monkeys. Neurology 28:1026–1036
Wahnschaffe U, Loescher W (1990) Effect of selective bilateral destruction of the substantia nigra on antiepileptic drug actions in kindled rats. Eur J Pharmacol 186:157–167
Posthypoxic Myoclonus in Rats
Fahn S (1986) Posthypoxic action myoclonus: literature review update. Adv Neurol 43:157–169
Jaw SP, Hussong MJ, Matsumoto RR, Truong DD (1994) Involvement of 5-HT2 receptors in posthypoxic stimulus-sensitive myoclonus in rats. Pharmacol Biochem Behav 49:129–131
Jaw SP, Dang T, Truong DD (1995) Chronic treatments with 5-HT1A agonists attenuate posthypoxic myoclonus in rats. Pharmacol Biochem Behav 52:577–580
Jaw SP, Nguyen B, Vuong QTV, Trinh TA, Nguyen M, Truong DD (1996) Effects of glutamate receptor antagonists in post-hypoxic myoclonus in rats. Brain Res Bull 40:163–166
Lance JW (1968) Myoclonic jerks and falls: aetiology, classification and treatment. Med J Aust 1:113–119
Lance W, Adams RD (1963) The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain 86:111–136
Truong DD, Matsumoto RR, Schwartz PH, Hussong MJ, Wasterlain CG (1994) Novel cardiac arrest model of posthypoxic myoclonus. Mov Disord 9:201–206
Rat Kainate Model of Epilepsy
Bardgett ME, Jackson JL, Taylor GT, Csernansky JG (1995) Kainic acid decreases hippocampal neuronal number and increases dopamine receptor binding in the nucleus accumbens: an animal model of schizophrenia. Behav Brain Res 70:153–164
Bolanos AR, Sarkisian M, Yang Y, Hori A, Helmers SL, Mikati M, Tandon P, Stafstrom CE, Holmes GL (1998) Comparison of valproate and phenobarbital treatment after status epilepticus in rats. Neurology 51:41–48
Bouilleret V, Ridoux V, Depaulis A, Marescaux C, Nehling A, LaSalles GLG (1999) Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience 89:717–729
Cilio MR, Bolanos AR, Liu Z, Schmid R, Yang Y, Stafstrom CE, Mikati MA, Holmes GL (2001) Anticonvulsant action and long-term effects of gabapentin in the immature brain. Neuropharmacology 40:139–147
Csernansky JG, Csernansky CA, Kogelman L, Montgomery EM, Bardgett ME (1998) Progressive neurodegeneration after intracerebroventricular kainic acid administration in rats: implications for schizophrenia? Biol Psychiatry 44:1143–1150
Ebert U, Brandt C, Löscher W (2002) Delayed sclerosis, neuroprotection, and limbic epileptogenesis after status epilepticus in the rat. Epilepsia 43(Suppl 5):86–95
Hellier JL, Patrylo PR, Buckmaster PS, Dudek FE (1998) Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy. Epilepsy Res 31:73–84
Hu RQ, Koh S, Torgerson T, Cole AJ (1998) Neuronal stress and injury in C57/BL mice after systemic kainic acid administration. Brain Res 810:229–240
Humphrey WM, Bardgett ME, Montgomery EM, Taylor GT, Csernanansky JG (2001) Methods for inducing neuronal loss in preweanling rats using intracerebroventricular infusion of kainic acid. Brain Res Protocol 7:1–10
Longo BM, Mello LEAM (1998) Supragranular mossy fiber sprouting in rat is not necessary for spontaneous seizures in the intrahippocampal kainate model epilepsy in the rat. Epilepsy Res 32:172–182
Madsen U, Stensbol TB, Krogsgaard-Larsen P (2001) Inhibitors of AMPA and kainate receptors. Curr Med Chem 8:1291–1301
Maj R, Fariello RG, Ukmar G, Varasi M, Pevarello P, McArthur RA, Salvati P (1998) PNU-151774E protects against kainate-induced status epilepticus and hippocampal lesions in the rat. Eur J Pharmacol 359:27–32
Pitkânen A, Nissinen J, Jolkkonen E, Tuunanan J, Halonen T (1999) Effects of vigabatrin treatment on status epilepticus-induced neuronal damage and mossy fiber sprouting in the rat hippocampus. Epilepsy Res 33:67–85
Tamagami H, Morimoto K, Watanabe T, Ninomiya T, Hirao T, Tanaka A, Kakumoto M (2004) Quantitative evaluation of central-type benzodiazepine receptors with [125I]Iomazenil in experimental epileptogenesis. I. The rat kainate model of temporal lobe epilepsy. Epilepsy Res 61:105–112
Pilocarpine Model of Epilepsy
André V, Ferrandon A, Marescaux C, Nehlig A (2001) Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy. Epilepsy Res 47:99–117
Arida RM, Sanabria ERG, da Silva AC, Faria LC, Scorza FA, Cavalheiro EA (2004) Physical training reverts hippocampal electrophysiological changes in rats submitted to the pilocarpine model of epilepsy. Physiol Behav 83:165–171
Biagini G, Avoli M, Marcinkiewicz J, Marcinkiewicz M (2001) Brain-derived neurotrophic factor superinduction parallels anti-epileptic-neuroprotective treatment in the pilocarpine epilepsy model. J Neurochem 76:1814–1822
Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L (1991) Long-term effects of pilocarpine in rats: structural damages of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32:778–782
Honchar MP, Olney JW, Sherman WR (1983) Systemic agents induce seizures and brain damage in lithium-treated rats. Science 220:323–325
Hort J, Brozek G, Mares P, Langmeier M, Komarek V (1999) Cognitive functions after pilocarpine-induced status epilepticus: changes during silent period precede appearance of spontaneous recurrent seizures. Epilpesia 40:1177–1183
Klitgaard H, Matagne A, Vanneste-Goemaere J, Margineanu G (2002) Pilocarpine-induced epileptogenesis in the rat: impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations. Epilepsy Res 51:93–107
Leite JP, Cavalheiro EA (1995) Effect of conventional antiepileptic drugs in a model of spontaneous recurrent seizures in rats. Epilepsy Res 20:93–104
Leite JP, Garcia-Cairasco N, Cavalheiro EA (2002) New insights from the use of pilocarpine and kainate models. Epilepsy Res 50:93–103
Leroy C, Poisbeau P, Keller AF, Nehlig A (2004) Pharmacological plasticity of GABAA receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy. J Physiol (Lond) 557:473–487
Löscher W (2002) Animal models for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res 50:105–123
Lyon A, Marone S, Wainman D, Weaver DF (2004) Implementing a bioassay to screen molecules for antiepileptogenic activity. Chronic pilocarpine versus subdural haematoma models. Seizure 13:82–86
Rigoulot MA, Koning E, Ferrandon A, Nehlig A (2004) Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy. J Pharmacol Exp Ther 308:787–795
Setkowicz Z, Ciarach M, Guzik R, Janeczko K (2004) Different effects of neuroprotectants FK-506 and cyclosporine A on susceptibility to pilocarpine-induced seizures in rats with brain injured at different developmental stages. Epilepsy Res 61:63–72
Tang FR, Chia SC, Chen PM, Gao H, Lee WL, Yeo TS, Burgunder JM, Probst A, Sim MK, Ling EA (2004) Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus. Epilepsy Res 59:167–180
Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L, Warter SM (1982) Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized nonconvulsive epilepsy. Neurosci Lett 33:97–101
Wallace MJ, Blair RE, Falenski KW, Martin BR, Delorenzo RJ (2003) The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 307:129–137
Self-Sustained Status Epilepticus
Barton ME, Klein BD, Wolf HH, White HS (2001) Pharmacological characterization of the 6Hz psychomotor seizure model of partial epilepsy. Epilepsy Res 47:217–227
Brandt C, Glien M, Potschka H, Volk H, Löscher W (2003) Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats. Epilepsy Res 55:83–103
Brown WC, Schiffman DO, Swinyard EA, Goodman LS (1953) Comparative assay of antiepileptic drugs by “psychomotor” seizure test and minimal electroshock threshold test. J Pharmacol Exp Ther 107:273–283
De Vasconcelos AP, Mazarati AM, Wasterlain CG, Nehlig A (1999) Self-sustaining status epilepticus after a brief electrical stimulation of the perforant path. A 2-deoxyglucose study. Brain Res 838:110–118
Halonen T, Nissinen J, Jansen JA, Pitkänen A (1996) Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus. Eur J Pharmacol 299:69–81
Halonen T, Nissinen J, Pitkänen A (1999) Neuroprotective effect of remacemide hydrochloride in a perforant pathway stimulation model of status epilepticus in the rat. Epilepsy Res 34:251–269
Halonen T, Nissinen J, Pitkänen A (2001) Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment of rats. Epilepsy Res 46:205–223
Laurén HB, Pitkänen A, Nissinen J, Soini SL, Korpi ER, Holopainen IE (2003) Selective changes in gamma-aminobutyric acid type A receptor subunits in the hippocampus in spontaneously seizing rats with chronic temporal lobe epilepsy. Neurosci Lett 349:58–62
Mazarati A, Liu H, Wasterlain C (1999) Opioid peptide pharmacology and immunocytochemistry in an animal model of self-sustaining status epilepticus. Neuroscience 89:167–173
Mazarati AM, Baldwin R, Klitgaard H, Matagne A, Wasterlain CG (2004) Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combination in experimental status epilepticus. Epilepsy Res 58:167–174
Nissinen J, Halonen T, Koivisto E, Pitkänen A (2000) A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat. Epilepsy Res 38:177–205
Pitkänen A, Tuumanen J, Halonen T (1996) Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala. Epilepsy Res 24:29–45
Walton NY, Jaing Q, Hyun B, Treiman DM (1996) Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. Epilepsy Res 24:19–28
Rat Model of Cortical Dysplasia
Aicardi J (1994) The place of neuronal migration abnormalities in child neurology. Can J Neurol Sci 21:185–193
Amano S, Ihara N, Umeura S (1996) Development of novel rat mutant with spontaneous limbic-like seizures. Am J Pathol 149:329–336
Baraban SC, Schwartzkroin PA (1995) Electrophysiology of CA1 pyramidal neurons in an animal model of neuronal migration disorders: prenatal methylazoxymethanol treatment. Epilepsy Res 22:145–156
Baraban SC, Schwartzkroin PA (1996) Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment. Epilepsy Res 23:189–194
Baraban SC, Wenzel HJ, Hochman DW, Schwartzkroin PA (2000) Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero. Epilepsy Res 39:87–102
Becker LE (1991) Synaptic dysgenesis. Can J Neurol Sci 18:170–180
Benardete EA, Kriegstein AR (2002) Increased excitability and decreased sensitivity to GABA in an animal model of dysplastic cortex. Epilepsia 43:970–982
Chevassus au Louis N, Baraban SC, Gaiarsa JL, Ben-Ari Y (1999) Cortical malformations and epilepsy: new insight from animal models. Epilepsia 40:811–821
Germano IM, Sperber EF (1997) Increased seizure susceptibility in adult rats with neuronal migration disorders. Brain Res 777:219–222
Hirotsune S, Fleck MW, Gambello MJ, Bix GJ, Chen A, Clark GD, Ledbetter DH, McBain CJ, Wynshaw-Boris A (1998) Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nat Genet 19:333–339
Jacobs KM (1996) Hyperexcitability in a model of cortical maldevelopment. Cereb Cortex 6:514–523
Jacobs KM, Prince DA (2005) Excitatory and inhibitory polysynaptic currents in a rat model of epileptogenic microgyria. J Neurophysiol 93:687–696
Jacobs KM, Hwang BJ, Pronce DA (1999) Focal epileptogenesis in a rat model of polymicrogyria. J Neurophysiol 81:159–173
Lee KS, Schottler F, Collins JL, Lanzino G, Couture D, Rao A, Hiramatsu KI, Goto Y, Hong SC, Caner H, Yamamoto H, Chen ZF, Bertram E, Berr S, Omary R, Scrable H, Jackson T, Goble J, Eisenman L (1997) A genetic animal model of human neocortical heterotypia associated with seizures. J Neurosci 17:6236–6242
Leré C, el Bahh B, La Salle GLG, Rougier A (2002) A model of “epileptic tolerance” for investigating neuroprotection, epileptic susceptibility and gene expression-related plastic changes. Brain Res Protocol 9:49–56
Morimoto K, Watanabe T, Ninomiya T, Hirao T, Tanaka A, Onishi T, Tamagami H (2004) Quantitative evaluation of central-type benzodiazepine receptors with [I125]Iomazenil in an experimental epileptogenesis: II. The rat cortical dysplasia model. Epilepsy Res 61:113–118
Smyth MD, Barbaro NM, Baraban SC (2002) Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res 50:251–264
Wenzel HJ, Robbins CA, Tsai LH, Schwartzkroin PA (2001) Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures. J Neurosci 21:983–998
Zhu WJ, Roper SN (2000) Reduced inhibition in an animal model of cortical dysplasia. J Neurosci 20:8925–8931
Genetic Animal Models of Epilepsy
Amano S, Ihara N, Uemura S, Yokoyama M, Ikeda M, Serikawa T, Sasahara M, Kataoka H, Hayase Y, Hazama F (1996) Development of a novel rat mutant with spontaneous limbic-like seizures. Am J Pathol 149:329–336
Bartoszewicz ZP, Noronha AB, Fujita N, Sato S, Bo L, Trapp BD, Quarles RK (1995) Abnormal expression and glycosylation of the large and small isoforms of myelinassociated glycoprotein in dysmyelinating quaking mutants. J Neurosci Res 41:27–38
Bartoszyk GD, Hamer M (1987) The genetic animal model of reflex epilepsy in the Mongolian gerbil: differential efficacy of new anticonvulsive drugs and prototype antiepileptics. Pharmacol Res Commun 19:429–440
Batini C, Teillet MA, Naquet R (2004) An avian model of genetic reflex epilepsy. Arch Ital Biol 142:297–312
Bouwman BM, van Rijn CM (2004) Effects of levetiracetam on spike and wave discharges in WAG/Rij rats. Seizure 13:591–594
Budziszewska B, Van Luijtelaar G, Coenen AML, Leźniewicz M, Lasoń W (1999) Effects of neurosteroids on spike-wave discharges in the genetic epileptic WAG/RiJ rat. Epilepsy Res 33:23–29
Chapman AG, Croucher MJ, Meldrum BS (1984) Evaluation of anticonvulsant drugs in DBA/2 mice with sound-induced seizures. Arzneim Forsch/Drug Res 34:1261–1264
Chapman AG, Durmüller N, Harrison BL, Baron BM, Parvez N, Meldrum BS (1995) Anticonvulsant activity of a novel NMDA/glycine site antagonist, MDL 104,653, against kindled and sound-induced seizures. Eur J Pharmacol 274:83–88
Chermat R, Doaré L, Lachapelle F, Simon P (1981) Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse. Naunyn-Schmiedeberg’s Arch Pharmacol 318:94–99
Coenen AML, Drinkenburg WHIM, Inoue M, Van Luijtelaar ELJM (1992) Genetic models of absence epilepsy, with emphasis on the WAG/RiJ strain of rats. Epilepsy Res 12:75–86
Collins RL (1972) Audiogenic seizures. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 347–372
Consroe P, Picchioni A, Chin L (1979) Audiogenic seizure susceptible rats. Fed Proc 38:2411–2416
Crawford RD (1969) A new mutant causing epileptic seizures in domestic fowl. Poult Sci 48:1799
Crawford RD (1970) Epileptic seizures in domestic fowl. J Hered 61:185–188
Cunningham JG (1971) Canine seizure disorders. J Am Vet Med Assoc 158:589–598
Dailey JW, Jobe PC (1985) Anticonvulsant drugs and the genetically epilepsy-prone rat. Fed Proc 44:2640–2644
Dailey JW, Reigel CE, Mishra PK, Jobe PC (1989) Neurobiology of seizure predisposition in the genetically epilepsy-prone rat. Epilepsy Res 3:3–17
Dailey JW, Yan QS, Adams-Curtis LE, Ryu JR, Ko KH, Mishra PK, Jobe PC (1996) Neurochemical correlation of antiepileptic drugs in the genetically epilepsy-prone rat. Life Sci 58:259–266
Danober L, Depaulis A, Vergnes M, Marescaux C (1995) Mesopontine cholinergic control over generalized non-convulsive seizures in a genetic model of absence epilepsy in the rat. Neuroscience 69:1183–1193
Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C (1998) Pathophysiological mechanisms of genetic absence epilepsy in the rat. Prog Neurobiol 55:27–57
Deransart C, Riban V, Lê BT, Marescaux C, Depaulis A (2000) Dopamine in the striatum modulates seizures in a genetic model of absence epilepsy in the rat. Neuroscience 100:335–344
Di Pasquale E, Keegan KD, Noebels JL (1997) Increase excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mouse stargazer. J Neurophysiol 77:621–631
Edmonds HL, Hegreberg GA, van Gelder NM, Sylvester DM, Clemmons RM, Chatburn CG (1979) Spontaneous convulsions in beagle dogs. Fed Proc 38:2424–2428
Faingold CL (1988) The genetically epilepsy-prone rat. Gen Pharmacol 19:331–338
Faingold CL, Naritoku DK (1992) The genetically epilepsy-prone rat: neuronal networks and actions of amino acid neurotransmitters. In: Faingold CL, Fromm GH (eds) Drugs for control of epilepsy: actions on neuronal networks involved in seizure disorders. CRC Press, Boca Raton, pp 277–308
Faingold CL, Randall ME, Boersma Anderson CA (1994) Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat. Exp Neurol 126:225–232
Famula TR, Oberbauer AM, Brown KN (1997) Heritability of epileptic seizures in the Belgian tervueren. J Small Anim Pract 38:349–352
Fletcher CF, Lutz CM, O’Sullivan TM, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel deficits. Cell 87:607–617
Galvis-Alonzo OY, Cortes de Oliveira JA, Garcia-Cairasco N (2004) Limbic epileptogenicity, cell loss and axonal reorganization induced by audiogenic and amygdala kindling in Wistar audiogenic rats (WAR strain). Neuroscience 125:787–802
Green RC, Seyfried TN (1991) Kindling susceptibility and genetic seizure predisposition in inbred mice. Epilepsia 32:22–26
Green MC, Sidman RL (1962) Tottering – a neuromuscular mutation in the mouse. J Hered 53:233–237
Heckroth JA, Abbott LC (1994) Purkinje cell loss from alternating sagittal zones in the cerebellum of leaner mutant mice. Brain Res 658:93–104
Herrup K, Wilczynsnki SL (1982) Cerebellar cell degeneration in the leaner mutant mouse. Neuroscience 7:2185–2196
Hogan EL (1977) Animals models of genetic disorders of myelin. In: Morell P (ed) Myelin. Plenum Press, New York, pp 489–520
Hosford DA, Lin FH, Wang Y, Caddick SJ, Rees M, Parkinson NJ, Barclay J, Cox RD, Gardiner RM, Hosford DA, Denton P, Wang Y, Seldin MF, Chan B (1999) Studies of the lethargic (Ih/lh) mouse model of absence seizures: regulatory mechanisms and identification of the gene. Adv Neurol 79:239–252
Iida K, Sasa M, Serikawa T, Noda A, Ishihara K, Akimitsu T, Hanaya R, Arita K, Kurisu K (1998) Induction of convulsive seizures by acoustic priming in a new genetically defined model of epilepsy (Noda epileptic rat: NER). Epilepsy Res 30:115–126
Imaizumi K, Ito S, Kutukake G, Takizawa T, Fujiwara K, Tutikawa K (1959) Epilepsy like anomaly of mice. Exp Anim (Tokyo) 8:6–10
Jobe PC, Mishira PK, Dailey JW (1992) Genetically epilepsy-prone rats: actions of antiepileptic drugs and monoaminergic neurotransmitters. In: Faingold CL, Fromm GH (eds) Drugs for control of epilepsy: actions on neuronal networks involved in seizure disorders. CRC Press, Boca Raton, pp 253–275
Jobe PC, Mishra PK, Adams-Curtis LE, Deoskar VU, Ko KH, Browning RA, Dailey JW (1995) The genetically epilepsy-prone rat (GEPR). Ital J Neurol Sci 16:91–99
Johnson DD, Davis HL, Crawford RD (1979) Pharmacological and biochemical studies in epileptic fowl. Fed Proc 38:2417–2423
Killam EK, Killam KF Jr (1984) Evidence for neurotransmitter abnormalities related to seizure activity in the epileptic baboon. Fed Proc 43:2510–2515
Killam KF, Naquet R, Bert J (1966) Paroxysmal responses to intermittent light stimulation in a population of baboons (Papio papio). Epilepsia 7:215–219
Killam KF, Killam EK, Naquet R (1967) An animal model of light sensitivity epilepsy. Electroencephalogr Clin Neurophysiol 22:497–513
King JT Jr, LaMotte CC (1989) El mouse as a model of focal epilepsy. Epilepsia 30:257–265
Ko KH, Dailey JW, Jobe PC (1982) Effect of increments of norepinephrine concentrations on seizure intensity in the genetically epilepsy-prone rat. J Pharmacol Exp Ther 222:662–669
Kuebler D, Tanouye MA (2000) Modification of seizure susceptibility in Drosophila. J Neurophysiol 83:998–1009
Kuebler D, Zhang H, Ren X, Tanouye MA (2001) Genetic suppression of seizure susceptibility in Drosophila. J Neurophysiol 86:1211–1225
Kurtz BS, Lehman J, Galick P, Amberg J, Mishra PK, Daikey JW, Weber R, Jobe PC (2001) Penetrance and expressivity of genes involved in the development of epilepsy in the genetically epilepsy-prone rat (GEPR). J Neurogenet 15:233–244
Laird HE 2nd (1989) The genetically epilepsy-prone rat. A valuable model for the study of epilepsies. Mol Chem Neuropathol 11:45–59
Lakaye B, Thomas E, Minet A, Grisar T (2002) The genetic absence epilepsy rat from Strasbourg (GAERS), a rat model of epilepsy: computer modeling and differential gene expression. Epilepsia 43(Suppl 5):123–129
Lee RJ, Lomax P (1984) The effect of spontaneous seizures on pentylenetetrazole and maximum electroshock induced seizures in the Mongolian gerbil. Eur J Pharmacol 106:91–98
Lee RJ, Hong JS, McGinty JF, Lomax P (1987) Increased enkephalin and dynorphin immunoreactivity in the hippocampus of seizure sensitive Mongolian gerbils. Brain Res 401:353–358
Letts VA, Mahaffey CL, Beyer B, Frankel WN (2005) A targeted mutation in Cacng4 exacerbates spike-wave seizures in stargazer (Cacng2) mice. Proc Natl Acad Sci U S A 102:2123–2128
Li W-X, Kuchler S, Zaepfel M, Badache A, Thomas D, Vincedon G, Baumann N, Zanetta JP (1993) Cerebellar soluble lectin and its glycoprotein ligands in the developing brain of control and dysmyelinating mutant mice. Neurochem Int 22:125–133
Löscher W (1984) Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review. Methods Find Exp Clin Pharmacol 6:531–547
Löscher W, Frey HH (1984) Evaluation of anticonvulsant drugs in gerbils with reflex epilepsy. Arzneim Forsch/Drug Res 34:1484–1488
Löscher W, Meldrum BS (1984) Evaluation of anticonvulsant drugs in genetic animal models of epilepsy. Fed Proc 43:276–284
Löscher W, Fisher JE Jr, Schmidt D, Fredow G, Honack D, Iturrian WB (1989) The sz mutant hamster: a genetic model of epilepsy or of paroxysmal dystonia? Mov Disord 4:219–232
Loskota WJ, Lomax P, Rich ST (1974) The gerbil as a model for the study of epilepsies. Epilepsia 15:109–119
Magalhães LHM, Garcia-Cairasco N, Massensini AR, Doretto MC, Moraes MFD (2004) Evidence for augmented brainstem activated forebrain seizures in Wistar Audiogenic rats subjected to transauricular electroshock. Neurosci Lett 369:19–23
Majkowski J, Kaplan H (1983) Value of Mongolian gerbils in antiepileptic drug evaluation. Epilepsia 24:609–615
Mitrovic N, Le Saux R, Gioanni H, Gioanni Y, Besson MJ, Maurin Y (1992) Distribution of [3H]clonidine binding sites in the brain of the convulsive mutant quaking mouse: a radioautographic analysis. Brain Res 578:26–32
Moraes MFD, Chavali M, Mishra PK, Jobe PC, Garcia-Cairasco N (2005) A comprehensive electrographic and behavioral analysis of generalized tonic-clonic seizures of GEPR-9s. Brain Res 1033:1–12
Naquet R, Meldrum BS (1972) Photogenic seizures in baboon. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy – a manual for the laboratory worker. Raven, New York, pp 373–406
Nehling A, Boehrer A (2003) Effects of remacemide in two models of genetically determined epilepsy, the GAERS and the audiogenic Wistar AS. Epilepsy Res 52:253–261
Nikulina EM, Skrinskaya JA, Avgustinovich DF, Popova NK (1995) Dopaminergic brain system in the quaking mutant mouse. Pharmacol Biochem Behav 50:333–337
Noda A, Hashizume R, Maihara T, Tomizawa Y, Ito Y, Inoue M, Kobayashi K, Asano Y, Sasa M, Serikawa T (1998) NER rat strain: a new type of genetic model in epilepsy research. Epilepsia 39:99–107
Noebels JL (1979) Analysis of inherited epilepsy using single locus mutations in mice. Fed Proc 38:2405–2410
Noebels JL, Sidman RL (1979) Inherited epilepsy: spike-wave and focal motor seizures in the mutant mouse tottering. Science 204:1334–1336
Noeberls JL, Qiao X, Bronson RT, Spencer C, Davisson MT (1990) Stargazer, a new neurological mutant in chromosome 15 in the mouse with prolonged cortical seizures. Epilepsy Res 7:129–135
Oberbauer AM, Grossmann DI, Irion DN, Schaffer AL, Eggleston ML, Famula TR (2003) The genetics of epilepsy in the Belgian tervuren and sheepdog. J Hered 94:57–63
Oguro K, Ito M, Tsuda H, Mutoh K, Shiraishi H, Shirasaka Y, Mikawa H (1991) Association of NMDA receptor sites and seizures E1 mice. Epilepsy Res 9:225–230
Patel S, Chapman AG, Graham JL, Meldrum BS, Frey P (1990) Anticonvulsant activity of NMDA antagonists, D(−)4-(3-phosphonopropyl)piperazine-2-carboxylic acid (D-CPP) and D(−)(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) in a rodent and a primate model of reflex epilepsy. Epilepsy Res 7:3–10
Quesney LF (1984) Pathophysiology of generalized photosensitive epilepsy in the cat. Epilepsia 25:61–69
Racine RJ, Steingart M, McIntyre DC (1999) Development of kindling-prone and kindling resistant rats: selective breeding and electrophysiological studies. Epilepsy Res 35:183–195
Reigel CE, Dailey JW, Jobe PC (1986) The genetically epilepsy-prone rat: an overview of seizure-prone characteristics and responsiveness to anticonvulsant drugs. Life Sci 39:763–774
Sarkisian MR, Rattan S, D’Mello SR, LoTurco LL (1999) Characterization of seizures in the flathead rat: a new genetic model in early postnatal development. Epilepsia 40:394–400
Sarkisova KY, Midzianovskaia IS, Kulikov MA (2003) Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy. Behav Brain Res 144:211–226
Sasa M, Ohno Y, Ujihara H, Fujita Y, Yoshimura M, Takaori S, Serikawa T, Yamada J (1988) Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat. Epilepsia 29:505–513
Scarlatelli-Lima AV, Magalhães LHM, Doretto MC, Moraes MFD (2003) Assessment of the seizure susceptibility of Wistar Audiogenic rat to electroshock, pentylenetetrazole and pilocarpine. Brain Res 960:184–189
Seki T, Matsubayashi H, Amano T, Kitada K, Serikawa T, Sakai N, Sasa M (2002) Adenoviral gene transfer of aspartoacyclase into the tremor rat, a genetic model of epilepsy, as a trial of gen therapy for inherited epileptic disorder. Neurosci Lett 328:249–252
Serikawa T, Yamada J (1986) Epileptic seizures in rats homozygous for two mutations, zitter and tremor. J Hered 77:441–444
Serikawa T, Ohno Y, Sasa M, Yamada J, Takori S (1987) A new model of petit mal epilepsy: spontaneous spike and wave discharges in tremor rats. Lab Anim 21:68–71
Serikawa T, Kogishi K, Yamada J, Ohno Y, Ujihara H, Fujita Y, Sasa M, Takaori S (1990) Long-term effects of continual intake of phenobarbital on the spontaneously epileptic rat. Epilepsia 31:9–14
Seyfried TN (1979) Audiogenic seizures in mice. Fed Proc 38:2399–2404
Seyfried TN, Glaser GH, Yu RK, Palayoor ST (1986) Inherited convulsive disorders in mice. Adv Neurol 44:115–133
Sidman M, Ray BA, Sidman RL, Klinger JM (1966) Hearing and vision in neurological mutant mice: a method for their evaluation. Exp Neurol 16:377–402
Smith SE, Dürmüller N, Meldrum BS (1991) The non-N-methyl-d-aspartate receptor antagonists, GYKI 52466 and NBQX are anticonvulsant in two animal models of reflex epilepsy. Eur J Pharmacol 201:179–183
Srenk P, Jaggy A, Gaillard C, Busato A, Horlin P (1994) Genetische Grundlagen der idiopathischen Epilepsie beim Golden Retriever. Tierärztl Prax 22:574–578
Stark LG, Killam KF, Killam EK (1970) The anticonvulsant effects of phenobarbital, diphenylhydantoin and two benzodiazepines in the baboon, Papio papio. J Pharmacol Exp Ther 173:125–132
Stenger A, Boudou JL, Briley M (1991) Anticonvulsant effect of some anxiolytic drugs on two models of sound-induced seizures in mice. In: Briley M, File SE (eds) New concepts in anxiety. McMillan Press, London, pp 326–331
Suzuki J (2004) Investigations of epilepsy with a mutant animal (EL mouse) model. Epilepsia 45(Suppl 8):2–5
Tacke U, Björk E, Tuomisto J (1984) The effect of changes in sound pressure level and frequency on the seizure response of audiogenic seizure susceptible rats. J Pharmacol Methods 11:279–290
Tehrani MH, Baumgartner BJ, Liu SC, Barnes EM Jr (1997) Aberrant expression of GABAA receptor subunits in the tottering mouse: an animal model for absence seizures. Epilepsy Res 28:213–223
Thiessen DD, Lindzey G, Friend HC (1968) Spontaneous seizures in the Mongolian gerbil (Meriones unguiculatus). Psychol Sci 11:227–228
Tsubota Y, Miyashita E, Miyajima M, Owada-Makabe K, Yukawa K, Maeda M (2003) The Wakayama epileptic rat (WER), a new mutant exhibiting tonic-clonic seizures and absence-like seizures. Exp Anim 52:53–62
Ujihara H, Renming X, Sasa M, Ishihara K, Fujita Y, Yoshimura M, Kishimoto T, Serikawa T, Yamada J, Takaori S (1991) Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats. Eur J Pharmacol 196:15–19
Van Luijtelaar ELJM, Coenen AML (1986) Two types of electrocortical paroxysms in an inbred strain of rats. Neurosci Lett 70:393–397
Van Luijtelaar ELJM, Budziszewska B, Tetich M, Lasoń W (2003) Finasteride inhibits the progesterone-induced spike-wave discharges in a genetic model of absence epilepsy. Pharmacol Biochem Behav 75:889–894
Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L, Warter SM (1982) Spontaneous paroxysmal electroclinical patterns in the rat: A model of generalized non-convulsive epilepsy. Neurosci Lett 33:97–101
Wang H, Burdette LJ, Frankel WN, Masukawa LM (1997) Paroxysmal discharges in the EL mouse, a genetic model of epilepsy. Brain Res 760:266–271
Xie R, Fujita Y, Sasa M, Ishihara K, Ujihara H, Takaori S, Serikawa T, Jamada J (1990) Antiepileptic effect of CNK-602A, a TRH analogue, in the spontaneously epileptic rat (SER), a double mutant. Jpn J Pharmacol 52(Suppl 1):290P
Zhang HG, Tan J, Reynolds E, Kuebler D, Faulhaber S, Tanouye M (2002) The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizures, paralysis and neuronal failure. Genetics 162:1283–1299
Transgenic Animals as Models of Epilepsy
Allen KM, Walsh CA (1999) Genes that regulate neuronal migration in the cerebral cortex. Epilepsy Res 36:143–154
Butler LS, Silva AJ, Abeliovich A, Watanabe Y, Tonegawa S, McNamara JO (1995) Limbic epilepsy in transgenic mice carrying a Cα 2+/calmodulin-dependent kinase II α-subunit mutation. Proc Natl Acad Sci U S A 92:6852–6855
Campbell KM, Veldman MB, McGrath MJ, Burton FH (2000) TS + OCD-like neuropotentiated mice are supersensitive to seizure induction. Neuroreport 11:2335–2338
Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, Horvath TL (2005) Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning. Endocrinology 144:5014–5021
Ferri AL, Cavallaro M, Braida D, Di-Christofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi PP, Sala M, DeBiasi S, Nicolis SK (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131:3805–3819
Giorgi FS, Pizzanelli C, Biagioni F, Murri L, Fornai F (2004) The role of epinephrine ion epilepsy: from the bench to the bedside. Neurosci Behav Rev 28:507–524
Kearney JA, Plummer NW, Smith MR, Kapur J, Cummins TR, Waxman SG, Goldin AR, Meisler MH (2001) A gain-of-function mutation in the sodium channel gene Scn2a results in seizures and behavioral abnormalities. Neuroscience 102:307–317
Knuesel I, Riban V, Zuellig RA, Schaub MC, Grady RM, Sanes JR, Fritschy JM (2002) Increase vulnerability to kainate-induced seizures in utrophin-knockout mice. Eur J Neurosci 15:1474–1484
Kokaia M, Holmberg K, Nanobashvili A, Xu ZQD, Kokaia Z, Lendahl U, Hilke S, Theodorsson E, Kahl U, Bartfai T, Lindvall O, Hökfelt T (2001) Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin. Proc Natl Acad Sci U S A 98:14006–14011
Kunieda T, Zuscik MJ, Boongird A, Perez DM, Luders HO, Najim IM (2002) Systemic overexpression of the alpha 1Badrenergic receptor in mice: an animal model of epilepsy. Epilepsia 43:1324–1329
Lahteinen S, Pitkanen A, Saarelainen T, Nissinen J, Koponen E, Castren E (2002) Decreased BDNF signaling in transgenic mice reduces epileptogenesis. Eur J Neurosci 15:721–734
Lahteinen S, Pitkanen A, Koponen E, Saarelainen T, Castren E (2003) Exacerbated status epilepticus and acute cell loss, but no changes in epileptogenesis, in mice with increased brain-derived neurotrophic factor signaling. Neuroscience 122:1081–1092
Lahteinen S, Pitkanen A, Knuuttila J, Toronen P, Castren E (2004) Brain-derived neurotrophic factor signaling modifies hippocampal gene expression during epileptogenesis in transgenic mice. Eur J Neurosci 19:3245–3254
Liang LP, Ho YS, Patel M (2000) Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience 101:563–570
Ludwig A, Budde T, Stieber J, Moosmang S, Langebartels A, Wotjak C, Munsch T, Zong X, Feil S, Feil R, Lancel M, Chien KR, Konnerth A, Pape HC, Biel M, Hofmann F (2003) Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2. EMBO J 22:216–224
Lüthi A, van der Putten H, Botteri FM, Mansuy IM, Meins M, Frey U, Sansig G, Portet C, Schmutz M, Schröder M, Nitsch C, Laurent JP, Monard D (1997) Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. J Neurosci 17:34688–34699
Mazarati A, Lu X, Shinmei S, Badie-Mahdavi H, Bartfai T (2004) Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GALR1) knockout mice. Neuroscience 128:431–441
Meldrum BS, Akbar MT, Chapman AG (1999) Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res 36:189–204
Musumeci SA, Bosco B, Calabrese G, Bakker C, De-Sarro GB, Elia M, Ferri R, Oostra BA (2000) Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 41:19–23
Noebels JL (1999) Single-gene models of epilepsy. Adv Neurol 79:227–238
Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D (2005) Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nat Neurosci 8:51–60
Potschka H, Krupp E, Ebert U, Gumbel C, Leichtlein C, Lorch B, Pickert A, Kramps S, Young K, Grune U, Keller A, Welschof M, Vogt G, Xiao B, Worley PF, Löscher W, Hiemisch H (2002) Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur J Neurosci 16:2157–2165
Prasad AN, Prasad C, Stafstrom CE (1999) Recent advances in the genetics of epilepsy: insights from human and animal studies. Epilepsia 40:1329–1352
Schauwecker PE (2002) Complications associated with genetic background effects in models of experimental epilepsy. Prog Brain Res 135:139–148
Shannon H, Yang L (2004) Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models. Epilepsy Res 61:49–62
Shimizu T, Ikegami T, Ogawara M, Suzuki Y, Takahashi M, Morio H, Shirasawa T (2002) Transgenic expression of the protein-l-isoaspartyl methyltransferase (PIMT) gene in the brain rescues mice from the fatal epilepsy of PIMT deficiency. J Neurosci Res 69:341–352
Toth M, Tecott L (1999) Transgenic approaches to epilepsy. Adv Neurol 79:291–296
Upton N, Stratton S (2003) Recent developments from genetic mouse models of epilepsy. Curr Opin Pharmacol 3:19–26
Viswanath V, Wu Z, Fonck C, Wei Q, Boonplueang R, Andersen JK (2000) Transgenic mice neuronally expressing baculoviral p35 are resistant to diverse types of induced apoptosis, including seizure-associated neurodegeneration. Proc Natl Acad Sci U S A 97:2270–2275
Weinshenker D, Szot P (2002) The role of catecholamines in seizure susceptibility: new results using genetically engineered mice. Pharmacol Ther 94:213–233
Yang Y, Frankel WN (2004) Genetic approaches to studying mouse model of human seizure disorders. Adv Exp Med Biol 548:1–11
Zeng Z, Kyaw H, Gakenheimer KR, Augustus M, Fan P, Zhang X, Su K, Carter KC, Li Y (1997) Cloning, mapping, and tissue distribution of a human homologue of the mouse jerky gene product. Biochem Biophys Res Commun 236:389–395
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Kallman, M.J. (2016). Anti-Epileptic Activity. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Cham. https://doi.org/10.1007/978-3-319-05392-9_28
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