A possible role of AA2 excitatory amino acid receptors in the expression of stimulant drug effects

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 sys...

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Bibliographic Details
Published in:Psychopharmacology 1990-01, Vol.101 (4), p.456-464
Main Authors: Freed, W J, Cannon-Spoor, H E
Format: Article
Language:English
Subjects:
2-Amino-5-phosphonovalerate - analogs & derivatives
6-Cyano-7-nitroquinoxaline-2,3-dione
Amino Acids - pharmacology
Amphetamine - pharmacology
Animals
Apomorphine - pharmacology
Behavior, Animal - drug effects
Central Nervous System Stimulants - pharmacology
Dibenzocycloheptenes - pharmacology
Dizocilpine Maleate
Dose-Response Relationship, Drug
Female
Glutamates - pharmacology
Mice
Motor Activity - drug effects
Phencyclidine - pharmacology
Quinoxalines - pharmacology
Receptors, Amino Acid
Receptors, Cell Surface - physiology
Stereotyped Behavior - drug effects
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Summary: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-phosphonoheptanoic acid (APH), or CNQX. APH decreased stereotypy only at a high dosage (250 mg/kg), which also produces ataxia. Several other compounds, including L-glutamic acid gamma ethyl ester (GMEE), L-glutamic acid, glycine, and L-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.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF02244222