Modifications of social conflict-induced analgesic and activity responses in male mice receiving chronic opioid agonist and antagonist treatments

Abstract

This study examined the effects of chronic (7 day) administration of opioid agonists and antagonists, via osmotic minipumps (20 μg/μl/h, or 2 mg/kg/h for each agent) on: 1) nociception and activity, and 2) the analgesic and locomotor responses of subordinate male mice experiencing social conflict (aggression without defeat) and defeat in a “resident-intruder” paradigm. Chronic infusion of the mu opioid antagonist, naltrexone, resulted in a hypoanalgesic response and a decrease in basal locomotor activity on days 3–7 postimplantation which returned to the basal levels of saline-implanted control mice after termination of the infusions on day 9. Naltrexone reduced defeat-induced analgesia on the second day after implantation, but had no consistent effects on analgesia on test days 6 and 9 or on the aggression-induced (nondefeat) analgesia and increases in activity. The delta opioid antagonist ICI-154, 129, while having no significant effects on basal nociception or locomotor activity, augmented nondefeat-induced analgesia (day 2) and reduced the defeat-induced increases in activity (days 2 and 6). The mu agonist, levorphanol, resulted in a significant analgesia on the first two days after infusion, followed by the development of tolerance to the analgesic effects over days 3–7. On day 9, a hypoanalgesic response indicative of withdrawal was evident. Levorphanol also induced a marked decrease in locomotor activity over days 3–7 postimplantation, with no evidence of the development of tolerance or withdrawal following termination of infusion. Levorphanol also enhanced the social conflict-induced analgesia on the second day of administration and attenuated defeat-induced analgesia and activity on day 6, with a return to basal response levels on day 9. The kappa opiate agonist, U-50, 488, resulted in initial analgesic responses and decreases in activity, followed over days 3–7 by the development of tolerance to both the analgesic and locomotor effects. On day 9, a hyperalgesia and increased activity, indicative of withdrawal were evident. On test day 6, during the tolerance phase, chronic U-50, 488 reduced the defeat-induced analgesic and locomotor responses with no consistent effects on the other test days. These results 1) demonstrate the differential nociceptive and locomotor consequences of chronic activation or blockade of mu, delta and kappa opiate receptors, and 2) indicate that mu, delta and kappa opioid systems are variably and likely synergistically involved in the expression of the analgesic and locomotor consequences of social conflict and defeat.