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 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.
Freed
W J
WJ
Preclinical Neurosciences Section, NIMH Neuroscience Center at Saint Elizabeths, Washington, DC 20032.
Cannon-Spoor
H E
HE
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects
D000596:Amino Acids; D000697:Central Nervous System Stimulants; D003986:Dibenzocycloheptenes; D005971:Glutamates; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C011829:glutamic acid diethyl ester; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000661:Amphetamine; D010622:Phencyclidine; D001058:Apomorphine; C031231:2-amino-7-phosphonoheptanoic acid