Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens.
The purpose of this study was to assess the role of endogenous dopamine and glutamate systems within the nucleus accumbens in modulating responses for oral ethanol reinforcements (10% w/v) in a free-choice operant task. Pretreatment with both systemic (100 micrograms/kg) and intra-nucleus accumbens microinjection of fluphenazine (2 and 4 micrograms), a dopamine receptor antagonist, significantly decreased responding for ethanol, without significantly affecting responses for water. Ethanol self-administration was also attenuated by microinjection into the nucleus accumbens of 2-amino-5-phosphopentanoic acid (AP-5, 3 and 6 micrograms), a competitive NMDA receptor antagonist. These results suggest that dopamine and glutamate neurotransmission in the nucleus accumbens may regulate ethanol self-administration and its reinforcing effects.
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
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Koob
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005476:Fluphenazine / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012646:Self Administration
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; D005476:Fluphenazine