Effects of punishment on choice between cocaine and food in rhesus monkeys

Rationale: Punishment is widely used in an effort to control drug-taking behavior; however, only a few preclinical studies have investigated the effects of punishment on drug self-administration. Such studies may contribute to more rational use of punishment to control drug use. Objectives: To evaluate the effects of punishment on choice between cocaine and food in rhesus monkeys. Methods: Rhesus monkeys were trained under a concurrent-choice schedule of food delivery (1 g pellets, fixed-ratio 100 schedule) or cocaine injections (0-0.1 mg/kg per injection, fixed-ratio 10 schedule). Full cocaine choice dose-effect curves were determined under baseline conditions and under test conditions in which a putative punisher (intravenous histamine injection; 0.0032-0.032 mg/kg per injection) was paired with either food or cocaine delivery. Results: Under baseline conditions, cocaine produced a dose-dependent increase in cocaine choice. Histamine functioned as a punisher of both food- and cocaine-maintained responding. Pairing histamine with food delivery reduced food choice, increased cocaine choice, and produced left shifts in the cocaine choice dose-effect curve. Conversely, pairing histamine with cocaine decreased cocaine choice, increased food choice, and produced right shifts in the cocaine choice dose-effect curve. The magnitude of histamine's punishing effects was directly related to histamine dose and probability of histamine delivery, and inversely related to the magnitude of-the reinforcer. Conclusions: These results demonstrate that a primary effect of punishment in the context of food vs cocaine choice is not only a decrease in the behavior being punished, but also an increase in the unpunished alternative behavior.