AMPA/kainate antagonists in the nucleus accumbens inhibit locomotor stimulatory response to cocaine and dopamine agonists.
The purpose of this study was to determine whether AMPA/kainate excitatory amino acid receptors in the nucleus accumbens (NAc) play a role in the locomotor stimulation produced by cocaine and dopamine receptor agonists. The stimulation of locomotor activity produced by the systemic administration of cocaine was markedly attenuated by either the D1 receptor antagonist SCH23390 or the D2 receptor antagonist eticlopride administered directly into the NAc. This indicates that both dopaminergic receptor subtypes in the NAc are involved in the motor stimulant response to cocaine. The intra-accumbens administration of DNOX or GAMS, which have been shown to inhibit the locomotor stimulation produced by the excitatory amino acid agonist AMPA, antagonized the locomotor stimulant response to cocaine administered either systemically or directly into the NAc. DNOX and GAMS also inhibited the stimulation of locomotor activity produced by the coinjection of the D1 agonist SKF38393 and the D2 agonist quinpirole injected into the NAc of normal animals and of animals pretreated with reserpine. These results suggest that the activation of AMPA/kainate receptors in the NAc plays an important role in the locomotor stimulation produced by cocaine and directly acting dopaminergic receptor agonists. The effects produced by the activation of these receptors is independent of endogenous dopamine stores, suggesting that these receptors are located postsynaptic to the dopaminergic nerve terminals.
Kaddis
F G
FG
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
Wallace
L J
LJ
Uretsky
N J
NJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007267:Injections; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003042:Cocaine; D004298:Dopamine; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D005973:Glutamine; D007608:Kainic Acid; D011810:Quinoxalines; D019257:Quinpirole; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C056723:FG 9041; C042626:gamma-glutamylaminomethylsulfonic acid