Skip to main content

Drug effects on learning and memory

  • Chapter
Drug Discovery and Evaluation

Abstract

It is easily understood that behavioral psychopharmacology faced with the task of dealing with extremely complex behavioral disturbances of the elderly certainly has difficulties in designing up appropriate analogue models in experimental animals for human aging or the deficits occurring during human aging. One of the major problems for experimental behavioral pharmacology is whether or not old animals are the appropriate models. At the first view it seems obvious that the study of potential geronto-psychopharmacologic drugs should be performed in old animals. However, the problem is much more complicated. Laboratory animals are not a homogenous population, especially when old. Most of these old animals who are one third survivors of a population have an individually different pathological history which is mostly unknown to the investigators. Some animals may be arthritic others may have bronchitis or cardiac deficiencies. If, for example, an arthritic rat is given a performance task associated with lever pressing, the animals may fail because of his rigid and painful joints and not because of a brain deficit or of the ineffectiveness of the test compound. Similar effects can be observed with old animals having a cataract in a visual discrimination task. Failure to perform a task may even be the result of both central and peripheral disturbances. Consequently it is impossible to describe the failure of one animal to perform the task to deficits in some parts of the brain or to pathological changes in the body.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bartus RT, Dean RL, Beer B (1980) Memory deficits in aged cebus monkeys and facilitation with central cholinomimetics. Neurobiol Aging 1: 145–152

    CAS  Google Scholar 

  • Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417

    PubMed  CAS  Google Scholar 

  • Bartus RT, Dean RL, Flicker C (1987) Cholinergic psycho-pharmacology: an integration of human and animal research on memory. In: Meltzer HY (ed) Psychopharmacology: The Third Generation of Progress. Raven Press, New York, pp 219–232

    Google Scholar 

  • Campbell BA, Spear NE (1972) Ontogeny of memory. Psycho! Rev 79: 215–236

    CAS  Google Scholar 

  • Christie JE, Shering A, Ferguson J, Glen AIM (1981) Physostigmine and arecoline: Effects of intravenous infusions in Alzheimer presenile dementia. Br J Psychiatry 138: 46–50

    Google Scholar 

  • Craik FJM (1977) Age differences in human memory. In: Birren JE, Schaie KW (eds., Handbook of the Psychology of Aging, Von Nostrand Reinhold Co., New York, NY, pp 384–420

    Google Scholar 

  • Davis KL, Mohs RC (1982) Enhancement of memory proc- esses in Alzheimer’s disease with multiple dose intrave-nous physostigmine. Am J Psychiatry 139: 1421–1424

    PubMed  CAS  Google Scholar 

  • Fisher A, Hanin I (1986) Potential animal models for senile dementia of Alzheimer’s type, with emphasis on AF64A-induced cholinotoxicity. Ann Rev Pharmacol Toxicol 26: 161–181

    CAS  Google Scholar 

  • Giurgea C, Mouravieff-Lesiusse F (1971) Pharmacological studies on an elementary model of learning - The fixation of an experience at spinal level: Part I: Pharmacological reactivity of the spinal cord fixation time. Arch Int Pharmacodyn 191: 279–291

    Google Scholar 

  • Giurgea C, Salama M (1977) Nootropic drugs. Progr NeuroPsychopharmac 1: 235–247

    Google Scholar 

  • Gold PE, McGaugh JL (1975) Changes in learning and memory during aging, In: Ordy JM, Brizzee KR (eds.), Neurobiology of Aging, Plenum Press, New York, NY, pp 145–158

    Google Scholar 

  • Gold PE, van Buskirk RB, McGaugh JL (1975) Age-related changes in learning and memory. In: Maletta G (ed.), A Survey Report on the Aging Nervous System, US Government Printing Office, Washington, DC, pp 169–178

    Google Scholar 

  • Hess EH (1972) “Imprinting” in a natural laboratory. Scientific American 227:24–31

    Google Scholar 

  • Hock FJ (1987) Drug influences on learning and memory in aged animals and humans. Neuropsychobiol 17: 145–160

    CAS  Google Scholar 

  • Jarvik ME (1964) Techniques for evaluating the effects of drugs on memory. In: Nodin JH, Siegler PE (eds) Animal and Clinical Pharmacologic Techniques in Drug Evaluation. Year Book Medical Publ. Inc.; Chicago, pp 339–347

    Google Scholar 

  • Kubanis P, Zornetzer SF (1981) Age-related behavioral and neurobiological changes: A review with emphasis on memory. Behay. neural Biol. 31: 115–172

    Google Scholar 

  • Lennenberg E (1967) The Biological Foundations of Language. Wiley & Sons, New York, NY

    Google Scholar 

  • Nordberg A (1990) Pharmacological modulation of transmitter activity in Alzheimer brains–an experimental model. In: Novel Therapeutic Strategies for Dementia Diseases. Acta Neur Scand, Suppl 129: 17–20

    Google Scholar 

  • Scheich H (1987) Neural correlates of auditory filial imprinting. J Comp Physiol A 161: 605–619

    PubMed  CAS  Google Scholar 

  • Schindler U, Rush DK, Fielding S (1984) Nootropic drugs: Animal models for studying effects on cognition. Drug Devel Res 4: 567–576

    Google Scholar 

  • Summers WE, Viesselman JO, March GM, Candelora K (1981) Use of THA in treatment of Alzheimer-like dementia. Pilot study in twelve patients. Biol Psychiatry 16: 145–153

    Google Scholar 

  • Sunderland T, Tariot PN, Newhouse PA (1988) Differential responsitivity of mood, behavior, and cognition to cholinergic agents in elderly, neuropsychiatric populations. Brain Res. Rev 13: 371–389

    Google Scholar 

  • Thal LJ, Fuld PA, Masur DM, Sharpless NS (1983) Oral physostigmine and lecithin improve memory in Alzheimer’s disease. Ann Neurology 13: 491–496

    CAS  Google Scholar 

  • Thompson G (1983) Rodent models of learning and memory in aging research. In Walker RF, Cooper RL (eds) Experimental and Clinical Interventions in Aging. Marcel Dekker, Inc., New York and Basel, pp 261–278

    Google Scholar 

  • Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K (1989) Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 57: 115–126

    PubMed  CAS  Google Scholar 

  • Atak JR, Perry EK, Bonham JR, Perry RH, Tomlinson BE, Blessed G, Fairbairn A (1983) Molecular forms of acetyl-cholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form. Neurosci Lett 40: 199–204

    Google Scholar 

  • Augustinsson KB (1971) Determination of activity of cholinesterases. In: Glick D (ed.) Methods of Biochemical Analysis, John Wiley & Sons, New York, pp 217–273

    Google Scholar 

  • Chan SL, Shirachi DY, Bhargava HN, Gardner E, Trevor AJ (1972) Purification and properties of multiple forms of brain acetylcholinesterase. J Neurochem 19: 2747–2758

    PubMed  CAS  Google Scholar 

  • Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 22: 3099–3108

    PubMed  CAS  Google Scholar 

  • Christie JE, Shering A, Ferguson J, Glen AIM (1981) Physostigmine and arecoline: Effects of intravenous infusions in Alzheimer presenile dementia. Br J Psychiatry 138: 46–50

    Google Scholar 

  • Davis KL, Mohs RC (1982) Enhancement of memory processes in Alzheimer’s disease with multiple dose intravenous physostigmine. Am J Psychiatry 139: 1421–1424

    PubMed  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88–95

    PubMed  CAS  Google Scholar 

  • Grassi J, Vigny M, Massoulié J (1982) Molecular forms of acetylcholinesterase in bovine caudate nucleus and superior cervical ganglion: solubility properties and hydrophobic character. J Neurochem 38: 457–469

    PubMed  CAS  Google Scholar 

  • Koelle GB, Koelle FS, Friedenwald JS (1950) The effect of inhibition of specific and non-specific cholinesterase. J Pharmacol Exp Ther 100: 180–191

    PubMed  CAS  Google Scholar 

  • McIntosh CHS, Plummer DT (1973) Multiple forms of acetyl- cholinesterase from pig brain. Biochem J 133: 655–665

    PubMed  CAS  Google Scholar 

  • Nachmansohn D, Rothenberg MA (1945) Studies on cholinesterase 1. On the specificity of the enzyme in nerve tissue. J Biol Chem 158: 653–666

    Google Scholar 

  • Rieger F, Vigny M (1976) Solubilization and physicochemical characterization of rat brain acetylcholinesterase: development and maturation of its molecular forms. J Neurochem 27: 121–129

    PubMed  CAS  Google Scholar 

  • Summers WE, Viesselman JO, March GM, Candelora K (1981) Use of THA in treatment of Alzheimer-like dementia. Pilot study in twelve patients. Biol Psychiatry 16: 145–153

    Google Scholar 

  • Taylor P (1980) Anticholinesterase agents, In: Gilman AG, Goodman LS, Gilman A. (eds) The Pharmacological Basis of Therapeutics, MacMillan Publishing Company, New York, pp 100–119

    Google Scholar 

  • Thal LJ, Fuld PA, Masur DM, Sharpless NS (1983) Oral physostigmine and lecithin improve memory in Alzheimer’s disease. Ann Neurology 13: 491–496

    CAS  Google Scholar 

  • Trevor AJ, Gordon MA, Parker KK, Chan SL (1978) Acetylcholinesterases. Life Sci 23: 1209–1220

    PubMed  CAS  Google Scholar 

  • Chemnitius J-M, Haselmeyer K-H, Zech R (1983) Brain cholinesterases: Differentiation of target enzymes for toxic organophosphorus compounds. Biochem Pharmacol 32: 1693–1699

    Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88–95

    PubMed  CAS  Google Scholar 

  • Walker CH, Mackness MI (1983) Esterases: Problems of identification and classification. Biochem Pharmacol 32: 3265–3269

    Google Scholar 

  • Christie JE, Shering A, Ferguson J, Glen AIM (1981) Physostigmine and arecoline: Effects of intravenous infusions in Alzheimer presenile dementia. Br J Psychiatry 138: 46–50

    Google Scholar 

  • Davis KL, Mohs RC (1982) Enhancement of memory process in Alzheimer’s disease with multiple dose intravenous physostigmine. Am. J. Psychiatry 139: 1421–1424

    Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88–95

    PubMed  CAS  Google Scholar 

  • Heilbronn E (1961) Inhibition of cholinesterase by tetrahydroaminacrin. A Chem Scand 15: 1386–1390

    CAS  Google Scholar 

  • Muller F, Dumez Y, Massoulié J (1985) Molecular forms and solubility of acetylcholinesterase during the embryonic development of rat and human brain. Brain Res 331: 295–302

    PubMed  CAS  Google Scholar 

  • O’Brien RD (1969) Phosphorylation and carbamylation of cholinesterase. Ann NY Acad Sci 160: 204–214

    PubMed  Google Scholar 

  • Sivam SP, Norris JC, Lim DK, Hoskins B, Ho IK (1983) Effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on mu scarinic, dopamine, and GABA receptors in the rat striatum. J Neurochem 40: 14141422

    Google Scholar 

  • Steinberg GM, Mednick ML, Maddox J, Rice R, Cramer J (1975) A hydrophobic binding site in acetylcholinesterase. J Med Chem 18: 1056–1061

    CAS  Google Scholar 

  • Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. New Eng J Med 315: 1241–1245

    Google Scholar 

  • Taylor P (1980) Anticholinesterase agents, In: Gilman AG, Goodman LS, Gilman A (eds.) The Pharmacological Basis of Therapeutics MacMillan Publishing Co., New York,. pp 100–119

    Google Scholar 

  • Thal LJ, Fuld PA, Masur DM, Sharpless NS (1983) Oral physostigmine and lecithin improve memory in Alzheimer’s disease. Ann Neurology 13: 491–496

    CAS  Google Scholar 

  • Yamada S, Isogai M, Okudaira H, Hayashi R (1983) Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine. J Pharmacol Exp Ther 226: 519525

    Google Scholar 

  • Damsa G, Westerink GHC, Horn AS (1985) A simple, sensitive, and economic assay for choline and acetylcholine using HPLC, an enzyme reactor, and an electrochemical detector. J Neurochem 45: 1649–1652

    Google Scholar 

  • DeBelleroche JS, Gardiner IM (1982) Cholinergic action in the nucleus accumbens: Modulation of dopamine and acetylcholine release. Br J Pharmacol 75: 359–365

    Google Scholar 

  • Drukarch B, Schepens E, Schoffelmeer ANM, Stoof JC (1989) Stimulation of D-2 dopamine receptors decreases the evoked in vitro release of [3H]-acetylcholine from rat neostriatum: Role of K. and Ca+2. J Neurochem 52: 1680–1685

    PubMed  CAS  Google Scholar 

  • Gibson GE, Peterson C (1981) Aging decreases oxidative metabolism and the release and synthesis of acetylcholine. J Neurochem 37: 978–984

    PubMed  CAS  Google Scholar 

  • Hadhazy P, Szerb JC (1977) The effect of cholinergic drugs on [3H] acetylcholine release from slices of rat hippocampus, striatum and cortex. Brain Res 123: 311–322

    PubMed  CAS  Google Scholar 

  • Harms HH, Wardeh G, Mulder AH (1979) Effects of adenosine on depolarization-induced release of various radiolabelled neurotransmitters from slices of rat corpus striatum. Neuropharmacol 18: 577–580

    CAS  Google Scholar 

  • Israel M. Lesbats B (1982) Application to mammalian tissue of the chemoluminescent method for detecting acetylcholine. J Neurochem 39: 248–250

    Google Scholar 

  • Jackson D, Stachowiak MK, Bruno JP, Zigmond MJ (1988) Inhibition of striatal acetylcholine release by endogenous serotonin. Brain Res 457: 259–266

    PubMed  CAS  Google Scholar 

  • James MK, Cubeddu LX (1984) Frequency-dependent muscarinic receptor modulation of acetylcholine and dopamine release from rabbit striatum. J Pharmacol Exp Ther 229: 98–104

    PubMed  CAS  Google Scholar 

  • James MK, Cubeddu LX (1987) Pharmacological characterization and functional role of muscarinic autoreceptors in the rabbit striatum. J Pharmacol Exp Ther 240: 203–214

    PubMed  CAS  Google Scholar 

  • Magnusson O, Nilsson LB, Westerlund D (1980) Simultaneous determination of dopamine, DOPC and homovanillic acid. Direct injections of supernatants from brain tissue homogenates in a liquid chromatography-electrochemical detection system. J Chromatogr 221: 237–247

    Google Scholar 

  • Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Aihara H (1988) Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of rat. Neuropharmacol 27: 603–609

    CAS  Google Scholar 

  • Nielsen JA, Johnston CA (1982) Rapid, concurrent analysis of dopamine, 5-hydroxytryptamine, their precursors and metabolites utilizing high performance liquid chromatography with electrochemical detection: analysis of brain tissue and cerebrospinal fluid. Life Sci 31: 2847–2856

    PubMed  CAS  Google Scholar 

  • Nishino N, Fuji Y, Kondo M, Shuntoh H, Fujiwara H, Tanaka C (1987) Effects of L-Threo-3,4,-dihydroxyphenylserine on efflux of monoamines and acetylcholine in guinea pig brain. J Pharmacol Exp Ther 242: 621–628

    PubMed  CAS  Google Scholar 

  • Parker EM, Cubeddu LX (1986) Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. I. Release in the absence of vesicular transmitter stores. J Pharmacol Exp Ther 237: 179–192

    Google Scholar 

  • Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25: 411–414

    PubMed  CAS  Google Scholar 

  • Raiteri M, Marchi M, Maura G (1984) Release of catecholamines, serotonin, and acetylcholine from isolated brain tissue. In: Lajtha A (ed) Handbook of Neurochemistry, 2nd ed, Plenum Press New York, London, pp 431–462

    Google Scholar 

  • Richardson IW, Szerb JC (1974) The release of labelled acetylcholine and choline from cerebral cortical slices stimulated electrically. Br J Pharmacol 52: 499–507

    PubMed  CAS  Google Scholar 

  • Robinson S (1983) Effect of 5HT-lesions on cholinergic neurons in the hippocampus, cortex and striatum. Life Sci 32: 345–353

    PubMed  CAS  Google Scholar 

  • Saijoh K, Fujiwara H, Tanaka C ( 1985 a) Influence of hypoxia on release and uptake of neurotransmitters in guinea pig striatal slices: Dopamine and acetylcholine. Jpn J Pharmacol 39: 529–539

    Google Scholar 

  • Saijoh K, Fujiwara H, Tanaka C (1985 b) Influence of hypoxia on release and acetylation of [3H]choline in brain slices from adult and newborn guinea pigs. Neurosci Lett 58: 371–374

    Google Scholar 

  • Schacht U, Leven M, Bäcker G (1977) Studies on brain metabolism of biogenic amines. Br J Clin Pharmacol 4: 77S - 87S

    PubMed  CAS  Google Scholar 

  • Sethy VH, Francis JW, Russell RR, Ruppel PL (1988) Dual effect of N-methyl-N-(1-methyl-4-pyrrolidino)-2-butyl) acetamide on release of (3H) acetylcholine from the rat hippocampal slices. Neuropharmacol 27: 1191–1195

    CAS  Google Scholar 

  • Smith CP, Huger FP, Petko W, Kongsamut S (1994) HP 749 enhances calcium-dependent release of [3H]norepinephrine from rat cortical slices and synaptosomes. Neurochem Res 19: 1265–1270

    PubMed  CAS  Google Scholar 

  • Smith CP, Petko WW, Kongsamut S, Roehr JE, Effland RC, Klein HT, Huger FP (1984) Mechanisms for the increase in electrically-stimulated norepinephrine (NE) release from cortical slices by HP 749 [N-(n-propyl)-N-(4-pyridinyl)1H-indol-1-amine]. Drug Dev Res 32: 13–18

    Google Scholar 

  • Smith CP, Petko WW, Kongsamut S, Roehr JE, Effland RC, Klein JT, Huger FP (1994) Mechanisms for the increase in electrically stimulated [3H]norepinephrine release from rat cortical slices by N-(n-propyl)-N-(4-pyridinyl)-1H-indol-Iamine. Drug Dev Res 32: 13–18

    CAS  Google Scholar 

  • Spignoli G, Pedata F, Giovannelli L, Banfi S, Moroni F, Pepeu G (1986) Effect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisition. Clin Neuropharmacol 9: S39 — S47

    PubMed  CAS  Google Scholar 

  • Stadler S, Nesselhut T (1986) Simple and rapid measurement of acetylcholine and choline by HPLC and enzymatic-electrochemical detection. Neurochem Int 9: 127–129

    PubMed  CAS  Google Scholar 

  • Strittmatter H, Jackisch R, Hertting G (1982) Role of dopamine receptors in the modulation of acetylcholine release in the rabbit hippocampus. Naunyn-Schmiedeberg’s Arch. Pharmacol. 321: 195–200

    Google Scholar 

  • Supavilai P, Karobath M (1985) Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex. Life Sci 36: 417–426

    PubMed  CAS  Google Scholar 

  • Szerb JC, Hadhazy P, Dudar JC (1977) Release of [3H]-acetylcholine from rat hippocampal slices: Effect of septal lesion and of graded concentrations of muscarinic agonists and antagonists. Brain Res 128: 285–291

    Google Scholar 

  • Wagner J, Palfreyman M, Zraika M (1979) Determination of DOPA, dopamine, DOPAC, epinephrine, norepinephrine, a-fluoromethylDOPA, and a-difluoromethylDOPA in various tissues of mice and rats using reversed-phase ion-pair liquid chromatography with electrochemical detection. J Chromatogr 221: 237–247

    Google Scholar 

  • Wagner J, Vitali P, Palfreyman MG, Zraika M, Huot S (1982) Simultaneous determination of 3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, dopamine, 4-hydroxy-3methoxyphenylalanine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5hydroxyindoleacetic acid in rat cerebrospinal fluid and brain by high-performance liquid chromatography with electrochemical detection. J Neurochem 38: 1241–1254

    PubMed  CAS  Google Scholar 

  • Zahniser NR, Penis J, Dwoskin LP (1986) Modulation of neurotransmitter release: an assay for receptor function. In: Chemical and functional assay of receptor binding. Soc Neurosci, Short Course 1, Syllabus, Washington, DC, pp 73–81

    Google Scholar 

  • Cho AK, Haslett WL, Jenden DJ (1962) The peripheral actions of oxotremorine, a metabolite of tremorine. J Pharmacol Exp Ther 138: 249–257

    PubMed  CAS  Google Scholar 

  • Bebbington A, Brimblecombe RW, Shakeshaft D (1966) The central and peripheral activity of acetylenic amines related to oxotremorine. Br J Pharmacol 26: 56–57

    CAS  Google Scholar 

  • Aronstam RS, Abood LG, Hoss W (1978) Influence of sulfhydryl reagents and heavy metals on the functional state of the muscarinic acetylcholine receptor in rat brain. Mol Pharmacol 14: 575–586

    PubMed  CAS  Google Scholar 

  • Birdsall NJM, Burgen ASV, Hulme EC (1978) The binding of agonists to brain muscarinic receptors. Mol Pharmacol 14: 723–736

    PubMed  CAS  Google Scholar 

  • Hulme EC, Birdsall NJM, Burger ASV, Mehta P (1978) The binding of antagonists to muscarinic receptors. Mol Pharmacol 14: 737–750

    PubMed  CAS  Google Scholar 

  • Sokolovsky M, Gurwitz D, Galron R (1980) Muscarinic receptor binding in mouse brain: regulation by guanine nucleotides. Biochem Biophys Res Commun 94: 487–492

    PubMed  CAS  Google Scholar 

  • Watson M, Roeske WR, Yamamura HI (1982) [3H]Pirenzepine selectively identifies a high affinity population of muscarinic cholinergic receptors in the rat cerebral cortex. Life Sci 31: 2019–2023

    Google Scholar 

  • Ringdahl B, Jenden DJ (1983) Minireview: Pharmacological properties of oxotremorine and its analogs. Life Sci 32: 2401–2413

    Google Scholar 

  • Olianas MC, Onali P, Neff NH, Costa E (1983) Adenylate cyclase activity of synaptic membranes from rat striatum: inhibition by muscarinic receptor agonists. Mol Pharmacol 23: 393–398

    PubMed  CAS  Google Scholar 

  • Smith CP, Huger FP (1983) Effect of zinc on [3H]-QNB displacement by cholinergic agonists and antagonists. Biochem Pharmacol 32: 377–380

    PubMed  CAS  Google Scholar 

  • Watson M, Roeske WR, Yamamura HI (1983 a) [3H]Pirenzepine selectively identifies a high affinity population of muscarinic cholinergic receptors in the rat cerebral cortex. Life Sci 31: 2019–2023

    Google Scholar 

  • Watson M, Yamamura HI, Roeske WR (1983 b) A unique regulatory profile and regional distribution of [3H]pirenzepine in the rat provide evidence for distinct M, and MZ muscarinic receptor subtypes. Life Sci 32: 3001–3011

    Google Scholar 

  • Brown JH, Brown SL (1984) Agonists differentiate muscarinic receptors that inhibit cyclic AMP formation from those that stimulate phosphoinositide metabolism. J Biol Chem 259: 3777–3781

    PubMed  CAS  Google Scholar 

  • Fisher SK, Figueirdo JC, Bartus R.J (1984) Differential stimulation of inositol phospholipid turnover in brain by analogs of oxotremorine. J Neurochem 43: 1171–1179

    PubMed  CAS  Google Scholar 

  • Marks MJ, O’Connor MF, Artman LD, Burch JB, Collins AC (1984) Chronic scopolamine treatment and brain cholinergic function. Pharmacol Biochem Behav 20: 771–777

    PubMed  CAS  Google Scholar 

  • Luthin GR, Wolfe BB (1984) Comparison of [3H]pirenzepine and [3H]quinuclidinylbenzilate binding to muscarinic cholinergic receptors in rat brain. J Pharmacol Exp Ther 228: 648–655

    PubMed  CAS  Google Scholar 

  • Nonaka R, Moroji T (1984) Quantitative autoradiography of muscarinic cholinergic receptors in the rat brain. Brain Res 296: 295–303

    PubMed  CAS  Google Scholar 

  • Ehlert FJ (1985) The relationship between muscarinic receptor occupancy and adenylate cyclase inhibitor in the rabbit myocardium. Mol Pharmacol 28: 410–421

    PubMed  CAS  Google Scholar 

  • El-Fakahani EE, Ramkumar V, Lai WS (1986) Multiple binding affinities of N-methylscopolamine to brain muscarinic acetylcholine receptors: differentiation from M, and MZ subtypes. J Pharmacol Exp Ther 238: 554–563

    Google Scholar 

  • Aronstam RS, Narayanan TK (1988) Temperature effect on the detection of muscarinic receptor-G protein interactions in ligand binding assays. Biochem Pharmacol 37: 1045–1049

    PubMed  CAS  Google Scholar 

  • McKinney M, Coyle JT (1991) The potential for muscarinic receptor subtype-specific pharmacotherapy for Alzheimer’s disease. Mayo Clinic Proc 66: 1225–1237

    CAS  Google Scholar 

  • Narahashi T (1992) Overview of toxins and drugs as tools to study excitable membrane ion channels: II. Transmitter activated channels. Meth Enzymol 207: 643–658

    PubMed  CAS  Google Scholar 

  • Berridge MJ (1987) Inositol trisphosphate and diacylglycerol: two interacting second messengers. Ann Rev Biochem 56: 159–193

    PubMed  CAS  Google Scholar 

  • Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315–321

    PubMed  CAS  Google Scholar 

  • Cockcroft S, Gomperts BD (1985) Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature 313: 534–536

    Google Scholar 

  • Conklin BR, Brann MR, Ma AL, Buckley NJ, Bonner TI, Axelrod J (1988) Stimulation of arachidonic acid release in transfected cells expressing cloned muscarinic receptors. Soc Neurosci Abst 14: 600

    Google Scholar 

  • Fisher SK, Agranoff BW (1987) Receptor activation and inositol lipid hydrolysis in neural tissues. J Neurochem 48: 999–1017

    PubMed  CAS  Google Scholar 

  • Fisher SK, Bartus RT (1985) Regional differences in the coupling of muscarinic receptors to inositol phospholipid hydrolysis in guinea pig brain. J. Neurochem. 45: 1085 1095

    Google Scholar 

  • Fisher SK, Domask LM, Roland RM (1989) Muscarinic receptor regulation of cytoplasmic Ca“ concentrations in human SK-N-SH neuroblastoma cells: Ca’ requirements for phospholipase C activation. Mol Pharmacol 35: 195–204

    Google Scholar 

  • Fisher SK, Figueiredo JC, Bartus RT (1984) Differential stimulation of inositol phospholipid turnover in brain by analogs of oxotremorine. J Neurochem 43: 1171–1179

    PubMed  CAS  Google Scholar 

  • Fisher SK, Klinger PD, Agranoff BW (1983) Muscarinic agonist binding and phospholipid turnover in brain. J Biol Chem 258: 7358–7363

    PubMed  CAS  Google Scholar 

  • Gusovsky F, Daly JW (1988) Formation of inositol phosphates in synaptoneurosomes of guinea pig brain: stimulatory effects of receptor agonists, sodium channel agents and sodium and calcium ionophores. Neuropharmacol 27: 95–105

    CAS  Google Scholar 

  • Gusovsky F, Hollingsworth EB, Daly JW (1986) Regulation of phosphatidylinositol turnover in brain synaptoneurosomes: Stimulatory effects of agents that enhance influx of sodium ions. Proc Natl Acad Sci USA 83: 3003–3007

    Google Scholar 

  • Gusovsky F, McNeal EZ, Daly JW (1987) Stimulation of phosphoinositide breakdown in brain synaptoneurosomes by agents that activate sodium influx: antagonism by tetrodotoxin, saxitoxin, and cadmium. Mol Pharmacol 32: 479–487

    PubMed  CAS  Google Scholar 

  • Heller Brown J, Brown SL (1984) Agonists differentiate muscarinic receptors that inhibit cyclic AMP formation from those that stimulate phosphoinositide metabolism. J Biol Chem 259: 3777–3788

    Google Scholar 

  • Heller Brown J, Goldstein D, Masters SB (1985) The putative M1 muscarinic receptor does not regulate phosphoinositide hydrolysis. Mol Pharmacol 27: 525–531

    Google Scholar 

  • Hirasawa K (1985) Phospatidylinositol turnover in receptor mechanisms and signal tranduction. Ann Rev Pharmacol Toxicol 25: 147–170

    CAS  Google Scholar 

  • Hirasawa K, Nishizuka Y (1985) Phosphatidylinositol turnover in receptor mechanism and signal transduction. Ann Rev Pharmacol Toxicol 25: 147–170

    CAS  Google Scholar 

  • Hokin LE and Hokin MR (1955) Effects of acetylcholine on the turnover of phosphoryl units in individual phospholipids of pancreas slices and brain cortex slices. Biochem Biophys Acta 18: 102–110

    PubMed  CAS  Google Scholar 

  • McKinney M (1993) Muscarinic receptor subtype-specific coupling to second messengers in neuronal systems. In; Cuello AC (ed) Progress in Brain Research, Vol 98, Chapter 40, pp 333–340

    Google Scholar 

  • Nahorski SR, Kendall DA, Batty 1 (1986) Receptors and phosphoinositide metabolism in the central nervous system. Biochem Pharmacol 35: 2447–2453

    CAS  Google Scholar 

  • Shapiro RA, Scherer NM, Habecker BA, Subers EM, Nathanson NM (1988) Isolation, sequence and functional expression of the mouse M1 muscarinic acetylcholine receptor gene. J Biol Chem 263: 18397–18403

    PubMed  CAS  Google Scholar 

  • Alkondon M, Albuquerque EX (1993) Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. J Pharmacol Exp Ther 265: 1455–1473

    Google Scholar 

  • Araujo DM, Lapchak PA, Collier B, Quirion R (1988) Characterization of N-[3H]methylcarbamylcholine on acetylcholine release in rat brain J. Neurochem 51: 292–299

    PubMed  CAS  Google Scholar 

  • Araujo DM, Lapchat PA, Robitaille Y, Gauthier S, Quirion R (1988) Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer’s disease. J Neurochem 50: 1914–1923

    PubMed  CAS  Google Scholar 

  • Balfour DJK (1982) The effects of nicotine on brain neurotransmitter systems. Pharmacol Ther 16: 269–282

    PubMed  CAS  Google Scholar 

  • Clarke PBS (1987) Nicotine and smoking: A perspective from animal studies. Psychopharmacology 92: 135–143

    PubMed  CAS  Google Scholar 

  • Connolly J, Boulter J, Heinemann SF (1992) a4–32 and other nicotinic acetylcholine receptor subtypes as targets of psychoactive and addictive drugs. Br J Pharmacol 105:657666

    Google Scholar 

  • Drasdo A, Caulfield M, Bertrand D, Bertrand S, Wonnacott(1992) Methyllycaconitine: a novel nicotinic antagonist. Mol Cell Neurosci 3: 237–243

    Google Scholar 

  • Karlin A (1991) Explorations of the nicotinic acetylcholine receptor. Harvey Lect 85: 71–107

    CAS  Google Scholar 

  • Lapchak PA, Araujo DM, Quirion R, Collier B (1989) Effect of chronic nicotine treatment on nicotinic autoreceptor function and N-[3H]methylcarbamylcholine binding sites in the rat brain. J Neurochem 52: 483–491

    PubMed  CAS  Google Scholar 

  • Luetje CW, Patrick J (1991) Both cc-and 13-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. J Neurosci 11: 837–845

    PubMed  CAS  Google Scholar 

  • Luetje CW, Wada K, Rogers S, Abramson SN, Tsuji K, Heinemann S, Patrick J (1990) Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations. J Neurochem 55: 632–640

    PubMed  CAS  Google Scholar 

  • Mulle C, Vidal C, Benoit P, Changeux JP (1991) Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system. J Neurosci 11: 2588–2597

    PubMed  CAS  Google Scholar 

  • Nordberg A, Winblad B (1986) Reduced number of [3H]nicotine and [3H]-acetylcholine binding sites in the frontal cortex of Alzheimer brains. Neurosci Lett 72: 115–119

    PubMed  CAS  Google Scholar 

  • Pabreza LA, Dhawan S, Kellar KJ (1991) [3H]Cytisine binding to nicotinic cholinergic receptors in brain. Mol Pharmacol 39: 9–12

    Google Scholar 

  • Role LW (1992) Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels. Curr Opin Neurobiol 2: 254. 262

    Google Scholar 

  • Sargent PB (1993) The diversity of neuronal nicotinic acetylcholine receptors. Annu Rev Neurosci 16: 403–443

    PubMed  CAS  Google Scholar 

  • Shimohama S, Taniguchi T, Fujiwara M, Kameyama M (1986) Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia. J Neurochem 46: 288–293

    PubMed  CAS  Google Scholar 

  • Sunderland T, Tariot PN, Newhouse PA (1988) Differential responsivity of mood, behavior and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res Rev 13: 371–389

    Google Scholar 

  • Vernalllis AB, Conroy WG, Berg DK (1993) Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes. Neuron 10: 451–464

    Google Scholar 

  • Whitehouse PJ, Martino AM, Wagster MV, Price DL, Mayeux R, Atack JR, Kellar KJ (1988) Reductions in [3H]nicotinic acetylcholine binding in Alzheimer’s disease and Parkinson’s disease: an autoradiographic study. Neurology 38: 720–723

    PubMed  CAS  Google Scholar 

  • Choi DW, Koh JY, Peters S (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci 8: 185–195

    PubMed  CAS  Google Scholar 

  • Dichter MA (1986) The pharmacology of cortical neurons in tissue culture. In:Electrophysiological Techniques in Pharmacology, Alan R. Liss, Inc., pp 121–147

    Google Scholar 

  • Furukawa S, Furukawa Y, Akazawa S, Satoyoshi E, Itoh K, Hayashi K (1983) A highly sensitive enzyme immunoassay for mouse ß nerve growth factor. J Neurochem 40: 734–744

    PubMed  CAS  Google Scholar 

  • Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K (1986) Synthesis and secretion of nerve growth factor by mouse astroglial cells in culture. Biochem Biophys Res Commun 136: 57–63

    PubMed  CAS  Google Scholar 

  • Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K (1987) Regulation of nerve growth factor synthesis/secretion by catecholamine in cultured mouse astroglial cells. Biochem Biophys Res Commun 147: 1048–1054

    PubMed  CAS  Google Scholar 

  • Graeber MB, Kreutzberg GW (1986) Astrocytes increase in glial fibrillary acidic protein during retrograde changes of facial motor neurons. J Neurocytol 15: 363–373

    PubMed  CAS  Google Scholar 

  • Hefti F (1986) Nerve growth factor promotes survival of septal cholinergic neurons after fibrial transsections. J Neurosci 6: 2155–2162

    PubMed  CAS  Google Scholar 

  • Kinoshita A, Yamada K, Hayakawa T (1991) Human recombinant superoxide dismutase protects primary cultured neurons against hypoxic injury. Pathobiol 59: 340–344

    CAS  Google Scholar 

  • Koh JY, Choi DW (1988) Vulnerability of cultured cortical neurons to damage by excitotoxins: Differential susceptibility of neurons containing NADPH-diaphorase. J Neurosci 8: 2153–2163

    Google Scholar 

  • Krieglstein J, Brungs H, Peruche B (1988) Cultured neurons for testing cerebroprotective drug effects in vitro. J Pharmacol Meth 20: 39–46

    CAS  Google Scholar 

  • Kromer LF (1987) Nerve growth factor treatment after brain injury prevents neuronal death. Science 235: 214–216

    PubMed  CAS  Google Scholar 

  • Lärkfors L, Ebendal T (1987) Highly sensitive immunoassays for fi-nerve growth factor. J Immunol Meth 97: 41–47

    Google Scholar 

  • Matsumoto T, Oshima K, Miyamoto A, Sakurai M, Goto M, Hayashi S (1990) Image analysis of CNS neurotrophic factor effects on neuronal survival and neurite outgrowth. J Neurosci Meth 31: 153–162

    CAS  Google Scholar 

  • Oberpichler-Schwenk H, Krieglstein J (1994) Primary cultures of neurons for testing neuroprotective drug effects. J Neural Transm (Suppl) 44: 1–20

    CAS  Google Scholar 

  • Ogura A, Miyamoto M, Kudo Y (1988) Neuronal death in vitro: parallelism between survivability of hippocampal neurons and sustained elevation of cytosolic Ca’ after exposure to glutamate receptor agonist. Exp Brain Res 73: 447458

    Google Scholar 

  • Peruche B, Ahlemeyer B, Brungs H, Krieglstein J (1990) Cultured neurons for testing antihypoxic drug effects. J Pharmacol Meth 23: 63–77

    CAS  Google Scholar 

  • Peruche B, Krieglstein J (1991) Neuroblastoma cells for testing neuroprotective drug effects. J Pharmacol Meth 26: 139–148

    CAS  Google Scholar 

  • Prehn JHM, Backhauß C, Krieglstein J (1993) Transforming growth factor-ß, prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo. J Cerebr Blood Flow Metab 13: 521–525

    CAS  Google Scholar 

  • Prehn JHM, Lippert K, Krieglstein J (1995) Are NMDA or AMPA/kainate receptor antagonists more efficacious in the delayed treatment of excitotoxic neuronal injury? Eur J Pharmacol 292: 179–189

    PubMed  CAS  Google Scholar 

  • Shinoda I, Furukawa Y, Furukawa S (1990) Stimulation of nerve growth factor synthesis/secretion by propentofylline in cultured mouse astroglial cells. Biochem Pharmacol 39: 1813–1816

    PubMed  CAS  Google Scholar 

  • Thoenen H, Barde YA (1980) Physiology of nerve growth factor. Physiol Rev 60: 1284–1355

    PubMed  CAS  Google Scholar 

  • White HS, Harmsworth WL, Sofia RD, Wof HH (1995) Felbamate modulates the strychnine-insensitive receptor. Epilepsy Res 20: 41–48

    PubMed  CAS  Google Scholar 

  • Williams LR, Varon S, Peterson GM, Wictorin K, Fischer W, Bjorklund A, Gage FH (1986) Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transsection. Proc Natl Acad Sci USA 83: 9231–9235

    PubMed  CAS  Google Scholar 

  • Yankner BA, Shooter EM (1982) The biology and mechanism of action of nerve growth factor. Ann Rev Biochem 51: 845–968

    PubMed  CAS  Google Scholar 

  • Yu ACH, Hertz E, Hertz L (1984) Alterations in uptake and release rates for GABA, glutamate, and glutamine during biochemical maturation of highly purified cultures of cerebral neurones, a GABAergic preparation. J Neurochem 42: 951–8960

    PubMed  CAS  Google Scholar 

  • Banati RB, Rothe G, Valet G, Kreutzberg GW (1991) Respiratory burst in brain macrophages: a flow cytometric study on cultured brain macrophages. Neuropath Appl Neurobiol 17: 223–230

    CAS  Google Scholar 

  • Banati RB, Schubert P, Rothe G, Rudolphi K, Valet G, Kreutzberg GW (1994) Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglial/brain macrophages by propentofylline. J Cerebr Blood Flow Metab 14: 145–149

    CAS  Google Scholar 

  • Bellavite P (1988) The superoxide-forming enzymatic system of phagocytes. Free Rad Biol Med 4: 255–261

    Google Scholar 

  • Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A (1987) Antigen presentation and tumor cytotoxicity by interferon-y-treated microglial cells. Eur J Immunol 17: 1271–1278

    PubMed  CAS  Google Scholar 

  • Giulian D, Baker TJ (1986) Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 6: 2163–2178

    PubMed  CAS  Google Scholar 

  • Rothe G, Oser A, Valet G (1988) Dihydrorhodamine 123: a new flow cytometric indicator for respiratory burst activity in neutrophil granulocytes. Naturwissensch 75: 354–355

    CAS  Google Scholar 

  • Rothe G, Valet G (1994) Flow cytometric assays of oxidative burst activity in phagocytes. Meth Enzymol 233: 539–548

    PubMed  CAS  Google Scholar 

  • Netto CA, Izquierdo I (1985) On how passive is inhibitory avoidance. Behav Neural Biol 43: 327–330

    PubMed  CAS  Google Scholar 

  • Chorover SL, Schiller PH (1965) Short-term retrograde amnesia in rats. J Comp Physiol Psychol 59: 73–78

    PubMed  CAS  Google Scholar 

  • Dilts SL, Berry CA (1967) Effect of cholinergic drugs on passive avoidance in the mouse. J Pharmacol Exp Ther 158: 279–285

    PubMed  CAS  Google Scholar 

  • Dunn RW, Flanagan DM, Martin LL, Kerman LL, Woods AT, Camacho F, Wilmot CA, Cornfeldt ML, Effland RC, Wood

    Google Scholar 

  • PL, Corbett R (1992) Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents. Eur J Pharmacol 214: 207–214

    Google Scholar 

  • Hudspeth WJ, McGaugh JL, Thomson CW (1964) Aversive and amnesic effects of electroconvulsive shock. J Comp Physiol Psycho] 57: 61–64

    CAS  Google Scholar 

  • Jarvik ME, Essmann WB (1960) A simple one-trial learning situation in mice. Psychol Rep 6: 290

    Google Scholar 

  • Kubanis P, Zornetzer SF (1981) Age-related behavioral and neurobiological changes: A review with emphasis on memory. Behav neural Biol 31: 115–172

    Google Scholar 

  • Lien EJ (1993) Design and discovery of new drugs by stepping-up and stepping-down approaches. Progr Drug Res 40: 163–189

    CAS  Google Scholar 

  • Zometzer SF, Thompson R, Rogers J (1982) Rapid forgetting in aged rats. Behav Neural Biol 36: 49–60

    Google Scholar 

  • Banfi S, Cornelli U, Fonio W, Dorigotti L (1982) A screening method for substances potentially active on learning and memory. J Pharmacol Meth 8: 255–263

    CAS  Google Scholar 

  • Fekete M, deWied D (1982) Potency and duration of action of the ACTH¢9 analog (ORG 2766) as compared to ACTH¢10 and [D-Phe’IACTH4_10 on active and passive avoidance behavior of rats. Pharmacol Biochem Behav 16: 387–392

    PubMed  CAS  Google Scholar 

  • Fine A, Dunnett SB, Björklund A, Iversen SD (1985) Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer disease. Proc Natl Acad Sci USA 82: 5227–5230

    PubMed  CAS  Google Scholar 

  • Fisher A, Brandeis R, Karton I, Pittel Z, Gurwitz D, Haring R, Sapir M, Levy A, Heldman E (1991) (±)-cis-2-Methylspiro(1,3-oxathiolane-5,3’)quinuclidine, an Ml selective cholinergic agonist, attenuates cognitive dysfunctions in an animal model of Alzheimer’s disease. J Pharmacol Exp Ther 257: 392–403

    Google Scholar 

  • Hock FJ (1994) Involvement of nitric oxide-formation in the action of losartan (DUP 753): effects in an inhibitory avoidance model. Behav Brain Res 61: 163–167

    PubMed  CAS  Google Scholar 

  • Hock FJ, Gerhards HJ, Wiemer G, Stechl J, Rüger W, Urbach H (1989) Effects of the novel compound, Hoe 065, upon impaired learning and memory in rodents. Eur J Pharmacol 171: 79–85

    PubMed  CAS  Google Scholar 

  • Hock FJ, McGaugh JL (1985) Enhancing effects of Hoe 175 on memory in mice. Psychopharmacology 86: 114–117

    PubMed  CAS  Google Scholar 

  • Jarvik ME, Kopp R (1967) An improved one-trial learning situation in mice. Psychol Rep 21: 221–224

    PubMed  CAS  Google Scholar 

  • King RA, Glasser RL (1970) Duration of electroconvulsive shock-induced retrograde amnesia in rats. Physiol Behav 5: 335–339

    PubMed  CAS  Google Scholar 

  • Rush DK, Streit K (1992) Memory modulation with peripherally acting cholinergic drugs. Psychopharmacology 106: 375–382

    PubMed  CAS  Google Scholar 

  • Wan R, Diamant A, de Jong W, de Wied D (1990) Changes in heart rate and body temperature during passive avoidance behavior in rats. Physiol Behav 47: 493–499

    PubMed  CAS  Google Scholar 

  • Bures J, Buresova 0 (1963) Cortical spreading depression as a memory disturbing factor. J Comp Physiol Psychol 56: 268–272

    CAS  Google Scholar 

  • Gouret C, Raynaud G (1976) Utilisation du test de la boite a deux compartiments pour la recherche de substances protégeant le rat contre l’amnésie par hypoxie: Intérèt at limites de la méthode. J Pharmacol (Paris) 7: 161–175

    Google Scholar 

  • Kurtz KH, Pearl J (1960) The effect of prior fear experience on acquired-drive learning. J Comp Physiol Psycho] 53: 201–206

    CAS  Google Scholar 

  • Staubli U, Huston JP (1978) Up-hill avoidance: A new passive avoidance task. Physiol Behav 21: 775–776

    Google Scholar 

  • Brioni JD (1993) Role of GABA during the multiple consolidation of memory. Drug Dev Res 28: 3–27

    CAS  Google Scholar 

  • Decker MW, Tran T, McGaugh JL (1990) A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice. Psychopharmacology 100: 515–521

    PubMed  CAS  Google Scholar 

  • Fine A, Dunnett SB, Bjorklund A, Iversen SD (1985): Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer’s disease. Proc Natl Acad Sci, USA 82: 5227–5230

    Google Scholar 

  • Hepler DJ, Wenk G, Cribbs BL, Olton DS, Coyle JT (1985) Memory impairments following basal forebrain lesions. Brain Res 346: 8–14

    PubMed  CAS  Google Scholar 

  • Kameyama T, Nabeshima T, Kozawa T (1986) Step-down-type passive avoidance-and escape-learning method. J Pharmacol Meth 16: 39–52

    CAS  Google Scholar 

  • Tomaz C, Dickinson-Anson H, McGaugh JL (1992): Basolateral amygdala lesions block diazepam-induced anterograde amnesia in an inhibitory avoidance task. Proc Natl Acad Sci USA 89: 3615–3619

    PubMed  CAS  Google Scholar 

  • Dilts SL, Berry CA (1976) Effects of cholinergic drugs on passive avoidance in the mouse. J Pharmacol Exper Ther 158: 279–285

    Google Scholar 

  • Drachman DA, Leavitt J (1974) Human memory and the cholinergic system. Arch Neurol 30: 113–121

    PubMed  CAS  Google Scholar 

  • Glick SD, Zimmerberg B (1972) Amnesic effects of scopolamine. Behav Biol 7: 245–254

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Lenègre A, Avril I, Doumont G (1988) Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. Psychopharmacology 95: 291–297

    PubMed  CAS  Google Scholar 

  • Schindler U, Rush DK, Fielding S (1984) Nootropic drugs: Animal models for studying effects on cognition. Drug Devel Res 4: 567–576

    Google Scholar 

  • Yamaoto T, Yatsugi SI, Ohno M, Furuya Y, Kitajima I, Ueki S (1990) Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats. Psychopharmacology 100: 316–322

    Google Scholar 

  • Connor DJ, Langlais PJ, Thal LJ (1991) Behavioral impairment after lesions of the nucleus basalis by ibotenic acid and quisqualic acid. Brain Res 555: 84

    PubMed  CAS  Google Scholar 

  • Dunnett SB, Whishaw IQ, Jones GH, Bunch ST (1989) Behavioral, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats. Neurosci 20: 653–669

    Google Scholar 

  • Fonnum F (1975) A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem 24: 407–409

    PubMed  CAS  Google Scholar 

  • Fuji K, Hiramatsu M, Hayashi S, Kameyama T, Nabeshima T (1993b) Effects of propentofylline, a NGF stimulator, on alterations in muscarinic cholinergic receptors induced by basal forebrain lesion in rats. Neurosci Lett 150: 99–102

    PubMed  CAS  Google Scholar 

  • Fuji K, Hiramatsu M, Kameyama T, Nabeshima T (1993a) Effects of repeated administration of propentofylline on memory impairment produced by basal forebrain lesion in rats. Eur J Pharmacol 236: 411–417

    PubMed  CAS  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motitiv 12: 239–260

    Google Scholar 

  • Chandler MJ, DeLeo JA, Carney JM (1985) An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes. J Pharmacol Meth 14: 137–146

    CAS  Google Scholar 

  • Gibson GE, Pulsinelli W, Blass JP, Duffy TE (1981) Brain dysfunction in mild to moderate hypoxia. Am J Med 70: 1247–1254

    PubMed  CAS  Google Scholar 

  • Levine S, Sohn D (1969) Cerebral ischemia in infant and adult gerbils. Arch Pathol 87: 315–317

    PubMed  CAS  Google Scholar 

  • Lundy EF, Solik BS, Frank RS, Lacy PS, Combs DJ, Zelenok GB, D’Alecy LG (1986) Morphometric evaluation of brain infarcts in rats and gerbils. J Pharmacol Meth 16: 201–214

    CAS  Google Scholar 

  • Schindler U (1983) The effect of graded cerebral ischemia on brain water content and learning ability in the Mongolian gerbil. J Cerebr Blood Flow Metab 3: S335 — S336

    Google Scholar 

  • Schindler U (1983) The effect of graded cerebral ischemia on brain water content and learning ability in the Mongolian gerbil. J Cerebr Blood Flow Metab 3: S335 — S336

    Google Scholar 

  • Schindler U, Rush DK, Fielding S (1984) Nootropic drugs: Animal models for studying effects on cognition. Drug Devel Res 4: 567–576

    Google Scholar 

  • Brush FR (1971) Aversive Conditioning and Learning. Academic Press, New York and London

    Google Scholar 

  • Campbell BA, Church RM (1969) Punishment and Aversive Behavior. Appleton-Century-Crofts, New York, NY

    Google Scholar 

  • D’Amato MR (1970) Experimental Psychology: Methodology, Psychophysics and Learning. McGraw-Hill, New York, NY, pp 381–416

    Google Scholar 

  • Herrnstein RJ (1969) Method and theory in the study of avoidance. Psychol Rev 76: 49–69

    PubMed  CAS  Google Scholar 

  • Capaldi EJ, Capaldi ED (1972) Aversive learning situations: apparatus and procedures. In: Myers RD (ed) Methods in Psychobiology, Vol. 2, Academic Press, London and New York, NY, pp 59–81

    Google Scholar 

  • Hock FJ, McGaugh JL (1985) Enhancing effects of Hoe 175 on memory in mice. Psychopharmacology 86: 114–117

    PubMed  CAS  Google Scholar 

  • Munn NL (1950) Handbook of Psychological Research on the Rat. Houghton Mifflin, Boston, MA

    Google Scholar 

  • Silverman P (1978) Conditioned avoidance of aversive stimuli. In: Animal behaviour in the laboratory. Chapman and Hall, London, pp 204–219

    Google Scholar 

  • Capaldi EJ, Capaldi ED (1972) Aversive learning situations: apparatus and procedures. In: RD. Myers (ed.), Methods in Psychobiology, Vol. 2, Academic Press, London and New York, NY, pp 59–81

    Google Scholar 

  • Netto CA, Valente JT, Borges-Sobrinho JB, Lasevitz J, Tomaz CA (1991) Reversal of retrieval impairment caused by retroactive interference in a two-way active avoidance task in rats. Behav Neur Biol 55: 114–122

    CAS  Google Scholar 

  • McKean DB, Pearl J (1968) Avoidance box for mice. Physiol Behav 3: 795–796

    Google Scholar 

  • Tenen SS (1966) An automated one-way avoidance box for the rat. Psychonom Sci 6: 407–408

    Google Scholar 

  • Gilbert RM (1969) Discrimination learning? In: Gilbert RM, Sutherland NS (eds) Animal Discrimination Learning. Academic Press, New York, NY and London, pp 455–498

    Google Scholar 

  • Hurwitz HMB (1969) Discrimination learning under avoidance schedules. In: Gilbert RM, Sutherland NS (eds) Animal Discrimination Learning. Academic Press, New York, NY and London, pp 413–454

    Google Scholar 

  • Siegel S (1969) Discrimination overtraining and shift behavior. In: Gilbert RM, Sutherland NS (eds) Animal Discrimination Learning. Academic Press, New York, NY and London, pp 187–213

    Google Scholar 

  • Sutherland NS (1969) Outlines of a theory of visual pattern recognition in animals and man. In: Gilbert RM, Sutherland NS (eds) Animal Discrimination Learning. Academic Press, New York, NY and London, pp 385–411

    Google Scholar 

  • Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in rat. J Comp Physiol Psycho! 93: 74–104

    CAS  Google Scholar 

  • Lamberty Y, Gower Ai (1990) Age-related changes in spontaneous behavior and learning in NMRI mice from maturity to middle age. Physiol Behav 47: 1137–1144

    PubMed  CAS  Google Scholar 

  • Sara SJ, Devauges V (1989) Idazoxan, an a-2 antagonist, facilitates memory retrieval in the rat. Behav Neural Biol 51: 401–411

    PubMed  CAS  Google Scholar 

  • Siegel S (1969) Discrimination overtraining and shift behavior. In: Gilbert RM, Sutherland NS (eds.) Animal Discrimination Learning, Academic Press, New York, NY, pp 187–213

    Google Scholar 

  • Buresova O, Bures J, Oitzl M, Zahalka A (1985): Radial maze in the water tank: an aversively motivated spatial working memory task. Physiol Behav 34: 1003–1005

    PubMed  CAS  Google Scholar 

  • Kesner R (1980): An attribute analysis of memory: the role of the hippocampus. Physiol Psychol 8: 189–197

    Google Scholar 

  • Kesner R (1986): Neurobiological views of memory, In: Martinez J, Kesner R (eds): Learning and Memory, Academic Press, Inc.: Orlando, pp 399–438

    Google Scholar 

  • Levin ED (1988): Psychopharmacological effects in the radial-arm maze. Neurosci Biobehav Rev 12: 169–175

    PubMed  CAS  Google Scholar 

  • Olton D, Walker J, Gage F (1978): Hippocampal connections and spatial discrimination. Brain Res 139: 295–308

    PubMed  CAS  Google Scholar 

  • Olton DS (1983) Memory functions and the hippocampus. In: Seifert W (ed) Neurobiology of the Hippocampus. Academic Press, London, New York, pp 335–373

    Google Scholar 

  • Olton DS, Becker J, Handelman G (1979): Hippocampus, space and memory. The Behavioral and Brain Sciences 2: 313–365

    Google Scholar 

  • Olton DS, Samuelson RJ (1976): Remembrance of places passed: spatial memory in rats. J Exp Psychol An Behav Proc 2: 97–116

    Google Scholar 

  • Grilsser OJ, Klinke R. (eds): Pattern Recognition in Biological and Technical Systems. Springer Verlag, Berlin ( 1971 ) Munn NL Handbook of Psychological Research on the Rat. Houghton Mifflin, Boston, MA (1950)

    Google Scholar 

  • Sutherland NS (1969) Outlines of a theory of visual pattern recognition in animals and man. In: Gilbert RM, Sutherland NS (eds.). Animal Discrimination Learning. Academic Press, New York, NY, pp 385–411

    Google Scholar 

  • Thompson R (1969) Localization of the `visual memory sys-tem’ in the white rat. J Comp Physiol Psychol 69: 1–29

    PubMed  Google Scholar 

  • Thompson R, Huestis PW, Crinella FM, Yu J (1987) Further lesion studies on the neuroanatomy of mental retardation in the white rat. Neurosci Biobehav Rev 11: 415–440

    PubMed  CAS  Google Scholar 

  • Brandeis R, Dachir S, Sapir M, Levy A, Fisher A (1990) Reversal of age-related cognitive impairments by an M1 cholinergic agent, AF102B. Pharmacol Biochem Behav 36: 89–95

    PubMed  CAS  Google Scholar 

  • Brioni JD, Arolfo MP, Jerusalinski D, Medina JH, Izquierdo I (1991): The effect of flumazenil on acquisition, retention and retrieval of spatial information. Behav Neural Biol 56: 329–335

    PubMed  CAS  Google Scholar 

  • Brioni JD, Decker MW, Gamboa LP, Izquierdo I, McGaugh JL (1990): Muscimol injections in the medial septum impair spatial learning. Brain Res 522: 227–234

    PubMed  CAS  Google Scholar 

  • Buresova O, Krekule I, Zahalka A, Bures J (1985): On-demand platform improves accuracy of the Morris water maze. J Neurosci Meth 15: 63–72

    CAS  Google Scholar 

  • Decker MW, Majchrzak MJ, Anderson DJ (1992): Effects of nicotine on spatial memory deficits in rats with spatial lesions. Brain Res 572: 281–285

    PubMed  CAS  Google Scholar 

  • Gallagher M, Burwell R, Burchinal M (1993): Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav Neurosci 107: 618–626

    PubMed  CAS  Google Scholar 

  • McNamara R, Skelton R (1993): The neuropharmacological and neurochemical basis of place learning in the Morris water maze. Brain Res Rev 18: 33–49

    PubMed  CAS  Google Scholar 

  • Morris R (1984): Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Meth 11: 4760

    Google Scholar 

  • Morris R, Anderson E, Lynch G, Baudry M (1986): Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist. Nature 319: 774–776

    PubMed  CAS  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motitiv 12: 239–260

    Google Scholar 

  • Morris RGM (1989): Synaptic plasticity and learning: Selective impairment in rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. J Neurosci 9: 3040–3057

    PubMed  CAS  Google Scholar 

  • Rapp PR, Rosenberg RA, Gallagher M (1987): An evaluation of spatial information processing in aged rats. Behay. Neurosci 101: 3–12

    Google Scholar 

  • Eichenbaum H, Otto T, Cohen NJ (1992): The hippocampuswhat does it do? Behay. Neural Biol 57: 2–36

    CAS  Google Scholar 

  • Lynch G, Stäubli U (1991): Possible contributions of longterm potentiation to the encoding and organization of memory. Brain Res Rev 16: 204–206

    Google Scholar 

  • Nigrosh BJ, Slotnik BM, Nevin JA (1957): Olfactory discrimination, reversal learning and stimulus control in rats. J Comp Physiol Psychol 89: 285–194

    Google Scholar 

  • Otto T, Schottler F, Stäubli U, Eichenbaum H, Lynch G (1991): Hippocampus and olfactory discrimination learning: effects of entorhinal cortex lesions on olfactory learning and memory in a successive-cue go-no-go task. Behav Neurosci 105: 111–119

    PubMed  CAS  Google Scholar 

  • Ravel N, Vigouroux M, Elaagouby A, Gervais R (1992): Scopolamine impairs delayed matching in an olfactory task in rats. Psychopharmacology 109: 439–443

    PubMed  CAS  Google Scholar 

  • Roman F, Han D, Baudry M (1989): Effects of two ACTH analogs on successive odor discrimination learning in rats. Peptides 10: 303–307

    PubMed  CAS  Google Scholar 

  • Roman FS, Simonetto I, Soumireu-Mourat B (1993): Learning and memory of odor-reward association: selective impairment following horizontal diagonal band lesions. Behav Neurosci 107: 72–81

    PubMed  CAS  Google Scholar 

  • Stäubli U, Ivy G, Lynch G (1984): Hippocampal denervation causes rapid forgetting of olfactory information in rats. Proc Natl Acad Sci, USA 81: 5885–5887

    Google Scholar 

  • Bantus RT (1979) Physostigmine and recent memory: Effects in young and aged non-human primates. Science 206: 1087–1089

    Google Scholar 

  • Bartus RT(1979) Effects of aging on visual memory, sensory processing and discrimination learning in the non-human primate. In: Ordy JM, Brizzee K (eds.) Aging. Vol. 10. Raven Press, New York, NY, pp 85–114

    Google Scholar 

  • Bartus RT, Dean RL (1981) Age-related memory loss and drug therapy: Possible directions based on animal models. In: Enna SJ, Samorajski T, Beer B (eds.) Aging Vol. 17. Raven Press New York, NY, pp 209–223

    Google Scholar 

  • Dean RL, Loullis C, Bartus RT (1983) Drug effects in an animal model of memory deficits in the aged: implications for future clinical trials. In: Walker RF, Cooper RL (eds) Experimental and Clinical Interventions in Aging. Marcel Dekker, New York, NY, pp 279–303

    Google Scholar 

  • Struble RG, Cork LC, Whitehouse PJ, Price DL (1982) Cholinergic innervation in neuritic plaques. Science 216: 413–414

    PubMed  CAS  Google Scholar 

  • Wisniewski HM, Ghetti T, Terry RD (1973) Neuritic (senile) plaques and filamentous changes in aged Rhesus monkeys. J Neuropathol Exp Neurol 32: 566–584

    PubMed  CAS  Google Scholar 

  • 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: R. Dingledine (ed.). Brain Slices, Plenum Press. New York, NY pp 381–437

    Google Scholar 

  • Bliss TVP, Lemo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232: 331–356

    PubMed  CAS  Google Scholar 

  • Dingledine RY, Dodd Y, Kelly JS (1980) The in vitro brain slice as a useful neurophysiological preparation for intracellular recording. J Neurosci Methods 2: 323–362

    PubMed  CAS  Google Scholar 

  • Kettenmann H, Grantyn R (eds.): Practical electrophysiological methods. Wiley-Liss, New York, NY (1992)

    Google Scholar 

  • Landfield PW, Deadwyler SA (eds) (1988): Long-term Potentiation: From Biophysics to Behavior. Alan R. Liss, Inc., New York, NY

    Google Scholar 

  • Mcllwain H, Rodnight R (1962) Preparing neural tissues for metabolic study in vitro. In: Mcllwain H, Rodnight R (eds.) Practical neurochemistry. Churchill Ltd. London, pp 109133

    Google Scholar 

  • Milner B (1972) Disorders of learning and memory after tem- poral lobe lesions in man. Clin Neurosurg 19: 421–446

    PubMed  CAS  Google Scholar 

  • Misgeld U (1992) Hippocampal Slices. In: Kettenmann H, Grantyn R (eds.): Practical electrophysiological methods. Wiley-Liss, New York, NY, pp 41–44

    Google Scholar 

  • Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20: 11–21

    PubMed  CAS  Google Scholar 

  • Tanak Y, Sakurai M, Goto M, Hayashi S (1990) Effect of xanthine derivatives on hippocampal long-term potentiation Teyler TJ (1980) Brain slice preparations: Hippocampus. Brain Res Bull 5: 391–403

    Google Scholar 

  • Barclay LL, Gibson GE, Blass PJ (1981) The string test: An early behavioral change in thiamine deficiency. Pharmacol Biochem Behav 14: 153–157

    Google Scholar 

  • Gibson GE, Blass JP (1976) Impaired synthesis of acetylcholine in brain accompanying mild hypoxia and hypoglycemia. J Neurochem 27: 37–42

    PubMed  CAS  Google Scholar 

  • Gibson GE, Pelmas CJ, Peterson C (1983) Cholinergic drugs and 4-aminopyridine alter hypoxic-induced behavioral deficits. Pharmacol Biochem Behav 18: 909–916

    PubMed  CAS  Google Scholar 

  • Gibson GE, Pulsinelli W, Blass JP, Duffy TE (1981) Brain dysfunction in mild to moderate hypoxia. Am J Med. 70: 1247–1254

    PubMed  CAS  Google Scholar 

  • Gibson GE, Shimada M, Blass JP (1978) Alterations in acetylcholine synthesis and cyclic nucleotides in mild cerebral hypoxia. J Neurochem 31: 757–760

    PubMed  CAS  Google Scholar 

  • Hock FJ (1993) Effects of cromakalim on sodium nitrite intoxication. In: Elsner N, Heisenberg M (eds.) Gene, Brain and Behaviour. Proceedings of the 21st Göttingen Neurobiology Conference. Georg Thieme Verlag, Stuttgart, 681

    Google Scholar 

  • Peterson C, Gibson GE (1982) 3,4-Diaminopyridine alters acetylcholine metabolism and behavior during hypoxia. J Pharmacol Exp Ther 222: 576–582

    Google Scholar 

  • Schindler U, Rush DK, Fielding S (1984) Nootropic drugs: Animal models for studying effects on cognition. Drug Develop Res 4: 567–576

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Vogel, H.G., Vogel, W.H. (1997). Drug effects on learning and memory. In: Vogel, H.G., Vogel, W.H. (eds) Drug Discovery and Evaluation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03333-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-03333-3_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-03335-7

  • Online ISBN: 978-3-662-03333-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics