Effects of drugs on food- and cocaine-maintained responding III: Dopaminergic antagonists

Abstract

 The effects of three dopamine (DA) antagonists (SCH23390, pimozide, and chlorpromazine), with various degrees of selectivity for D₁ and D₂ receptors, and an agonist (the cocaine analog, CFT) were studied on responding maintained under a multiple fixed-ratio (FR) 30 food, FR30 cocaine (1–100 µg/kg per injection) delivery, with an interposed 10-min time-out (TO), schedule in rhesus monkeys. The effects of each drug depended upon the unit dose of cocaine. With an intermediate (10 µg/kg per injection) unit dose of cocaine, each antagonist decreased rates of responding maintained by either event in a dose-related manner. At higher (56–100 µg/kg per injection) unit doses of cocaine, antagonists generally increased and then decreased both food- and cocaine-maintained responding in a dose-related manner. These increases appeared to result from the blockade of non-specific rate-decreasing effects of self-administered cocaine, questioning their relevance to the reinforcing effects of cocaine. The results failed to support a role for pharmacological selectivity in this rate-decreasing effect of cocaine, as both D₁ and D₂ antagonists were able to reverse the effect. In contrast, CFT decreased cocaine-maintained responding at doses less than those that decreased food-maintained responding, and failed to shift the cocaine dose-effect function to the left. These results, together with previous work, suggest that agonists can selectively decrease drug-seeking behavior.