Abstract
GDEE, an antagonist of the AA2 or quisqualic acid category of excitatory amino acid receptor, decreases behavioral activity and locomotor stimulation induced by cocaine and amphetamine when locally injected into the nucleus accumbens. The present experiment was intended to examine the effects of systemic GDEE and other excitatory amino acid antagonists on stimulant-induced locomotor activity. GDEE markedly attenuated the stimulant effect of amphetamine, and partially blocked the effects of phencyclidine (PCP). Apomorphine-induced cage climbing behavior was partially decreased by lower dosages of GDEE, but was almost completely blocked by the highest dosage tested. Amphetamine-induced stimulation of locomotor activity was not decreased by any of the other excitatory amino acid antagonists that were tested, including MK-801, 2-amino-7-phosphonophetanoic acid (APH), or CNQX. APH decreased stereotypy only at a high dosage (250 mg/kg), which also produces ataxia. Several other compounds, includingl-glutamic acid gamma ethyl ester (GMEE),l-glutamic acid, glycine, andl-glutamine did not block amphetamine-induced stimulation in molar dosages equivalent to the highest dosage of GDEE (8 mmol/kg). It is concluded that the AA2 excitatory amino acid receptor is important in the expression of activating effects of stimulant drugs.
Similar content being viewed by others
References
Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum. Brain Res 302:267–275
Carter CJ (1982) Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats. Neuropharmacology 21:379–383
Carter CJ, L'Heureuz R, Scatton B (1988) Differential control by N-methyl-d-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study. J Neurochem 51:462–468
Chang HH, Michaelis EK, Roy S (1984) Functional characteristics ofl-glutamate, N-methyl-d-asparate and kainate receptors in isolated brain synaptic membranes. Neurochem Res 9:903–915
Clark WG, Vivonia CA, Baxter CF (1968) Accurate freehand injection into the lateral brain ventricle of the conscious mouse. J Appl Physiol 25:319–321
Donzati BA, Uretsky NJ (1983) Effects of excitatory amino acids on locomotor activity after bilateral microinjection into the rat nucleus accumbens: possible dependence on dopaminergic mechanisms. Neuropharmacology 22:971–981
Donzati BA, Uretsky NJ (1984) Antagonism of the hypermotility response induced by excitatory amino acids in the rat nucleus accumbens. Naunyn Schmiedeberg's Arch Pharmacol 325:1–7
Fielding S, Lal H (1978) Behavioral actions of neuroleptics. In: Iverson LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. vol. 10. Neuroleptics and schizophrenia. Plenum Press, New York, pp 91–128
Foster AC, Fagg GE (1988) Acidic amino acid receptor nomenclature: time for a change. Trends Neurosci 11:17–18
Freed WJ (1985) Selective inhibition of homocysteine-induced seizures by glutamic acid diethyl ester and other glutamate esters. Epilepsia 26:30–36
Freed WJ (1989a) Impaired motor coordination in mice induced by 2-amino-7-phosphonoheptanoic acid (APH), glutamic acid diethyl ester (GDEE) and other compounds. Pharmacol Biochem Behav 32:733–736
Freed WJ (1989b) An hypothesis regarding the antipsychotic effect of neuroleptic drugs. Pharmacol Biochem Behav 32:337–345
Freed WJ, Michaelis EK (1978) Glutamic acid and ethanol dependence. Pharmacol Biochem Behav 8:509–514
Freed WJ, Wyatt RJ (1981) Impairment of instrumental learning in rats by glutamic acid diethyl ester. Pharmacol Biochem Behav 14:223–226
Freed WJ, Weinberger DR, Bing LA, Wyatt RJ (1980) Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice. Psychopharmacology 71:291–297
Freed WJ, Bing LA, Wyatt RJ (1984) Effects of neuroleptics on phencyclidine (PCP)-induced locomotor stimulation in mice. Neuropharmacology 23:175–181
Freed WJ, Cannon-Spoor HE, Rodgers CR (1989) Attenuation of the behavioral response to quisqualic acid and glutamic acid diethyl ester by chronic haloperidol administration. Life Sci 44:1303–1308
Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase immunoreactive boutons in synaptic contact with identified striatonigral neurons with particular reference to dendritic spines. Neuroscience 13:1189–1215
Harris KM, Miller RJ (1989) CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) antagonizes NMDA-evoked [3H]-GABA release from cultured cortical neurons via an inhibitory action at the strychnine-insensitive glycine site. Brain Res 489:185–189
Herrling PL (1985) Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: evidence for its mediation by quisqualate- or kainate-receptors. Neuroscience 14:417–426
Herrling PL, Morris R, Salt TE (1983) Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurones. J Physiol 339:207–222
Hicks TP, Hall JG, McLennan H (1978) Ranking of excitatory amino acids by the antagonists glutamic acid diethyl ester andd-α-aminoadipic acid. Can J Physiol Pharmacol 56:901–907
Honore T, Davies SN, Drejer J, Fletcher EJ, Jacobsen P, Lodge D, Nielsen FE (1988) Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241:701–703
Jurson PA, Freed WJ (1990) A slight anticonvulsant effect of CNQX and DNQX as measured by homosysteine- and quisqualate-induced seizures. Pharmacol Biochem Behav 36:177–181
Kelly PH, Iversen SD (1976) Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant induced locomotor activity in rats. Eur J Pharmacol 40:45–56
Kelly PH, Seviour P, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522
Kemp JM, Powell TPS (1970) The cortico-striate projection in the monkey. Brain 93:525–546
Krogsgaard-Larsen P, Hansen JJ, Lauridsen J, Peet MJ, Leah JD, Curtis DR (1982) Glutamic acid agonists, stereochemical and conformational studies ofDl-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and related compounds. Neurosci Lett 31:313–317
Mayer ML, Westbrook GL (1987) The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28:197–276
McGeer PL, McGeer EG, Scherer U, Singh K (1977) A glutamatergic corticostriatal path? Brain Res 128:369–373
McLennan H (1975) Excitatory amino acid receptors in the central nervous system. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol. 4. Amino acid neurotransmitters. Plenum Press, New York, pp 211–228
McLennan H (1983) Receptors for the excitatory amino acids in the mammalian central nervous system. Prog Neurobiol 20:251–271
Michaelis EK, Michaelis ML, Stormann TM, Chittenden WL, Grubbs RD (1983) Purification and molecular characterization of the brain synaptic membrane glutamate-binding protein. J Neurochem 40:1742–1753
Mogenson GJ, Nielsen M (1984a) A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity. Behav Neural Biol 42:51
Mogenson GJ, Nielsen M (1984b) Neuropharmacological evidence that the nucleus accumbens and subpallidal region contribute to exploratory locomotion. Behav Neural Biol 42:52–60
Monaghan DJ, 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
Olsen RW, Szamraj O, Houser CR (1987) [3H]AMPA binding to glutamate receptor subpopulations in rat brain. Brain Res 402:243–254
Protais P, Costentin J, Schwartz JC (1976) Climbing behavior induced by apomorphine in mice: a simple test for the study of dopamine receptors in striatum. Psychopharmacology 50:1–6
Pulvirenti L, Swerdlow NR, Koob GF (1989) Microinjection of a glutamate antagonist into the nucleus accumbens reduces psychostimulant locomotion in rats. Neurosci Lett 103:213–218
Roberts PJ, Anderson SD (1979) Stimulatory effect ofl-glutamate and related amino acids on 3H-dopamine release from rat striatum: an in vitro model for glutamate actions. J Neurochem 2:1539–1545
Rudolph MI, Arqueros L, Bustos G (1983)l-glutamic acid, a neuromodulator of dopaminergic transmission in the rat corpus striatum. Neurochem Int 5:479–486
Sanberg PR, Hagenmeyer SH, Henault M (1985) Automated measurement of multivariant locomotor behavior in rodents. Neurobehav Toxicol Teratol 17:87–94
Sanger DJ, Jackson A (1989) Effects of phencyclidine and other N-methyl-d-aspartate antagonists on the schedule-controlled behavior of rats. J Pharmacol Exp Ther 248:1215–1221
Schmidt WJ (1986) Intrastriatal injection ofDl-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine. Psychopharmacology 90:123–130
Schmidt WJ, Bubser M (1989) Anticataleptic effects of the N-methyl-d-aspartate antagonist MK-801 in rats. Pharmacol Biochem Behav 32:621–623
Schwarz SS, Freed WJ (1986) Inhibition of quisqualate-induced seizures by glutamic acid diethyl ester and anti-epileptic drugs. J Neural Transm 67:191–203
Segal M (1976) Glutamate antagonists in rat hippocampus. Br J Pharmacol 58:341–345
Shreve PE, Uretsky NJ (1988) Role of quisqualic acid receptors in the hypermotility response produced by the injection of AMPA into the nucleus accumbens. Pharmacol Biochem Behav 30:379–384
Spencer HJ (1976) Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: evidence of glutamic acid as an excitatory transmitter in rat striatum. Brain Res 102:91–101
Stone TW (1973) Cortical pyramidal tract neurones and their sensitivity tol-glutamic acid. J Physiol (Lond) 233:211–255
Stone WE, Javid MJ (1984) Effects of anticonvulsant and other agents on seizures induced by intracerebrall-glutamate. Brain Res 264:165–167
Sturgeon RD, Fessler RG, London SF, Meltzer HY (1981) A comparison of the effects of neuroleptics on phencyclidine-induced behaviors in the rat. Eur J Pharmacol 76:37–53
Swerdlow NR, Veccarino FJ, Amalri M, Koob GF (1986) The neural substrates for the motor-activating properties of psychostimulants: a review of recent findings. Pharmacol Biochem Behav 25:233–248
Toth E, Lajtha A (1988) Motor effects of intracaudate injection of excitatory amino acids. Pharmacol Biochem Behav 33:175–179
Walaas I (1988) Biochemical evidence for overlapping neocortical and allocortical glutamate projections to nucleus accumbens and rostral caudatoputamen in the rat brain. Neuroscience 6:399–405
Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21:165–204
Webster, KE (1965) Cortico-striatal interrelations in the albino rat. J Anat 95:532–544
Wong EHF, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL (1986) The anticonvulsant MK-801 is a potent N-methyl-d-aspartate antagonist. Proc Natl Acad Sci USA 83:7104–7108
Young AMJ, Bradford HF (1986) Excitatory amino acid neuro-transmitters in the corticostriate pathway: studies using intracerebral microdialysis in vivo. J Neurochem 47:1399–1404
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Freed, W.J., Cannon-Spoor, H.E. A possible role of AA2 excitatory amino acid receptors in the expression of stimulant drug effects. Psychopharmacology 101, 456–464 (1990). https://doi.org/10.1007/BF02244222
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244222