IS EPIBATIDINE REALLY ANALGESIC - DISSOCIATION OF THE ACTIVITY, TEMPERATURE, AND ANALGESIC EFFECTS OF(+ -)-EPIBATIDINE/

The experiments in the present study were designed to determine if the activity, temperature, and analgesic effects of (+/-)-epibatidine tre atment could be dissociated. Initially (i.e., 15 min) (+/-)-epibatidin e treatment (0.1 mu mol/kg = 28 mu g/kg, IP) impaired rotorod performa nce, decreased activity, decreased temperature, and increased jump lat ency (e.g., analgesic effect). For the remaining time points measured (i.e., 30, 60, and 120 min), activity and temperature remained signifi cantly reduced. In contrast, by 120 min (+/-)-epibatidine's effects on rotorod performance and analgesia (jump latency) were not observed. W hen administered after (+/-)-epibatidine (0.05 mu mol/kg, IP), mecamyl amine treatment (5 mu mol/kg = 1 mg/kg, IP) produced a potentiation of analgesia. This potentiation effect was not observed on activity and temperature measures. The effect of (+/-)epibatidine treatment (0.1 mu mol/kg, IP) was also determined in mice with central nicotinic recept or blockade induced by treatment with chlorisondamine (23 mu mol/kg = 10 mg/kg, IP). An (+/-)-epibatidine-induced reduction in activity was not attenuated in chlorisondamine-treated mice and only a minimal effe ct was observed on (+/-)-epibatidine-induced hypothermia in chlorisond amine-treated mice. In contrast, in chlorisondamine-treated mice (+/-) -epibatidine's analgesic effect was attenuated. Taken together, these data suggest that various centrally mediated effects of (+/-)-epibatid ine can be dissociated.