alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonists in the nucleus accumbens and ventral pallidum decrease the hypermotility response to psychostimulant drugs.
The purpose of this study was to determine the role of alpha-amino-3-hydroxy- 5-methylisoxazole-4-propionate (AMPA)/kainate excitatory amino acid receptors in the nucleus accumbens and the ventral pallidum in the hypermotility responses to amphetamine, caffeine and scopolamine. To accomplish this, we determined the effects of intracranial injections of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and gamma-D-glutamylaminomethyl-sulfonate (GAMS), which inhibit the responses to AMPA, quisqualate and kainate in electrophysiological and behavioral studies. The bilateral administration of either DNQX (1 micrograms/0.5 microliters) or GAMS (5 micrograms/0.5 microliters) into the nucleus accumbens inhibited the locomotor stimulation produced by amphetamine (0.5 mg/kg s.c.) but not by caffeine (20 mg/kg s.c.) or scopolamine (0.5 mg/kg s.c.). However, the bilateral administration of either of the two antagonists into the ventral pallidum inhibited the response to all three stimulants. The administration of 6-amino-7-fluroquinoxaline-2,3-dione, a chemical analog of DNQX that does not bind to AMPA receptors, into either the nucleus accumbens or the ventral pallidum did not inhibit the locomotor stimulation produced by amphetamine. Neither DNQX nor GAMS injected into either the nucleus accumbens or the ventral pallidum produced significant changes in the locomotor activity of animals not injected with the stimulants. These results suggest that activation of AMPA/kainate receptors in the nucleus accumbens is important in the stimulation of locomotion produced by amphetamine, whereas activation of these receptors in the ventral pallidum is involved in the hypermotility response to all three central nervous system stimulants.
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus.
D L
DL
Willins
L J
LJ
Wallace
D D
DD
Miller
N J
NJ
Uretsky
D000818:Animals; D001921:Brain / Q000187:drug effects*; D005917:Globus Pallidus / Q000187:drug effects*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005973:Glutamine; D007051:Ibotenic Acid; D007608:Kainic Acid; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C056723:FG 9041; C042626:gamma-glutamylaminomethylsulfonic acid