A novel choice method for studying drugs as punishers.

In contrast to reinforcing effects, little is known about the neurobehavioral pharmacology of aversive effects of drugs that may limit their self-administration. The present study was designed to develop a novel choice method for studying drugs as punishers. Rhesus monkeys (n=4) were trained in a two-lever choice procedure. During a trial, completion of a variable-ratio 10 (VR10) schedule on one lever resulted in the simultaneous injection of a drug and delivery of two food pellets. Completion of an independent VR10 on the other lever resulted in simultaneous delivery of a saline injection and two food pellets. Reinforcer delivery ended a trial and began a time-out (TO) of 10 min. Sessions ended after approximately 4 h. When a preference was observed, injection/lever pairings were reversed to ensure reinforcer preference. When the drug injection was histamine (0.0015-0.006 mg/kg/injection), preference for the drug+food option decreased in a dose-related manner to near 0% in all monkeys. Effective doses of histamine were approximately 10-fold lower than in previously published experiments. In contrast, when the drug was cocaine (0.012-0.2 mg/kg/injection), preference for the drug+food option increased in a dose-related manner to near 100% in all monkeys. Choice may be a sensitive and selective method for studying aversive effects of drugs.