Intravenous self-administration of cocaine and norcocaine by dogs.

The potency of cocaine, relative to d-amphetamine, to initiate and maintain intravenous self-administration behavior by dogs (n = 5) was determined. Response-contingent infusions of cocaine (at unit doses of 0.15, 0.30 and 0.60 mg/kg/infusion) and d-amphetamine (at unit doses of 0.05 and 0.10 mg/kg/infusion) were available during daily 4-h sessions on a FR1 reinforcement schedule. By comparing the dose-response curves of the two drugs, it was found that 1 mg of amphetamine is equivalent to 5.3 mg of cocaine (95% confidence limits = 3.8--9.1 mg). In a second experiment, pretreatment with the alpha-adrenergic antagonist phenoxybenzamine (in doses ranging from 0.125--2.0 mg/kg, IV) did not produce any appreciable changes in responding for cocaine (0.2 mg/kg/infusion) by dogs (n = 9). In contrast, when the same animals were pretreated with the dopaminergic antagonist pimozide (in doses ranging from 5--40 mg/kg, IV), subsequent responding for cocaine was increased in a dose-dependent manner. In a third experiment it was determined that norcocaine, the N-demethylated metabolite of cocaine, would maintain self-administration behavior by dogs (n = 4) when it was substituted for cocaine. As expected, when saline was substituted for cocaine, responding was not maintained.