Effects of a D1 and a D2 dopamine antagonist on the self-administration of cocaine and piribedil by rhesus monkeys.
Rhesus monkeys were surgically prepared with chronic intravenous catheters and allowed to self-administer the indirect dopamine (DA) agonist cocaine (0.03 or 0.1 mg/kg/inj) or the direct D2 agonist piribedil (0.1 or 0.2 mg/kg/inj) on a fixed-ratio 10 schedule of drug delivery during daily 2 hour experimental sessions. When responding was stable, they were injected IV with SCH 23390, a selective D1 antagonist (0.003-0.3 mg/kg, 30 min pre-session) or pimozide, a selective D2 antagonist (0.003-0.3 mg/kg, 2 hours pre-session). Intermediate doses of pimozide generally increased self-administration of cocaine or piribedil, though increases in piribedil self-administration were more reliable. In contrast, intermediate doses of SCH 23390 either did not affect or decreased cocaine and piribedil self-administration. High doses of each antagonist decreased the rate of self-administration of each compound and produced catalepsy. The selective increase in responding maintained by cocaine or piribedil following pimozide pretreatment suggests a role for a D2-like receptor in psychomotor stimulant self-administration.
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010868:Pimozide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010891:Piribedil / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*; D012646:Self Administration
D014150:Antipsychotic Agents; D001552:Benzazepines; D010879:Piperazines; D011954:Receptors, Dopamine; D010868:Pimozide; D010891:Piribedil; D003042:Cocaine