title: Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food.
abstract: The hypothesis that mesolimbic dopamine is selectively involved in cocaine reinforcement was investigated in the rat. Animals were trained under a multiple schedule in which responding was reinforced by intravenous cocaine (0.75 mg/kg/injection) or food (45-mg pellets) under fixed-ratio 15 schedule requirements in alternate 30-min components of a 2-hr daily session. Infusion of the catecholaminergic neurotoxin 6-hydroxydopamine, but not the vehicle solution, into the region of the nucleus accumbens and olfactory tubercle produced selective reductions in cocaine self-administration without significantly altering responding maintained by food within the same sessions. This effect was reproduced in intact animals by substituting saline for cocaine in the self-administration component. These results support the hypothesis that the reinforcing effects of cocaine are dependent upon mesolimbic dopamine and demonstrate that cocaine self-administration can be disrupted in animals without altering behavior maintained by a nondrug reinforcer.
authors.affiliation: Department of Neuropharmacology, CVN-7, Scripps Research Institute, La Jolla, California 92037.
authors.forename: S B
authors.initials: SB
authors.lastname: Caine
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000378:metabolism*; D018492:Dopamine Antagonists; D004435:Eating; D009714:Nucleus Accumbens / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018492:Dopamine Antagonists; D016627:Oxidopamine; D003042:Cocaine