A novel choice method for studying drugs as punishers.

摘要

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 dosesof 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.