Analgesia and decrement in operant performance in socially defeated mice: selective cross-tolerance to morphine and antagonism by naltrexone.

Abstract

During a social confrontation between a resident and an intruder mouse, only the submissive or defeated intruder shows an opioid-mediated analgesia to which tolerance develops. We investigated the altered morphine responsiveness after different kinds of social experiences. Mice were assessed for performance of operant behavior under the control of a fixed ratio schedule of positive reinforcement as well as for the tail flick response to a heat stimulus before and after one or five consecutive social confrontations. The dose-effect curves for morphine's suppression of schedule-controlled behavior were closely similar before and after defeat in a single or in five social confrontations. However, the concurrently measured response to pain in the tail flick assay produced morphine dose-effect curves that were shifted to the right after defeat in one or five social confrontations. Four to six times higher doses of morphine were necessary to produce analgesia in mice that were defeated in five social confrontations. Naltrexone (1 mg/kg, ip) antagonized the suppressive effects of morphine (10 mg/kg, ip) on rate of responding and the analgesic effects. Naltrexone also blocked the development of analgesia in mice that were defeated for the first time in a social confrontation, but did not prevent the suppressive effects on rate of responding. Specific social experiences such as defeat in a social confrontation appear to alter endogenous opioid process that mediate analgesia; these processes differ from those that suppress positively reinforced behavior. The differential development of morphine tolerance to the analgesic effects, but not the rate-decreasing effects as well as the differential naltrexone antagonism of both effects may indicate the involvement of opioid and non-opioid mechanisms.