Effects of dopamine D-1 and D-2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat.
The effects of three dopamine D-1 receptor antagonists (SCH23390, SCH39166 and A69024) and three dopamine D-2 antagonists (raclopride, eticlopride and spiperone) on cocaine self-administration maintained under different schedules of reinforcement were examined in the rat. Intravenous cocaine self-administration was maintained under a fixed-ratio (FR) 5 schedule with a 20-sec timeout (TO) after each reinforcement or a FR 15 with a 2-min TO multiple schedule of cocaine (0.25 mg i.v.) and food (45 mg) reinforcement. With the exception of raclopride, all of the antagonists altered the self-administration of cocaine in a manner similar to decreasing the unit dose of cocaine under the schedule in effect, reflected by increased self-administration under the FR 5 TO 20-sec schedule and decreased self-administration under the FR 15 TO 2-min multiple schedule. Moreover, a low dose of either of the benzazepine dopamine D-1 antagonists SCH23390 or SCH39166, but not the other compounds, selectively reduced cocaine self-administration without altering responding for food under the multiple schedule. Conversely, a low dose of raclopride or A69024 selectively decreased food-reinforced responding without altering cocaine self-administration under the multiple schedule. These results suggest that benzazepine dopamine D-1 antagonists, at low doses, may attenuate the reinforcing properties of cocaine more selectively than other dopamine receptor antagonists. The results also demonstrate the advantages of using different schedules to investigate the effects of dopamine D-1 and D-2 antagonists on cocaine self-administration.
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Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
Koob
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012054:Reinforcement, Psychology; D012646:Self Administration
D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine