Potentiation of kappa-opioid receptor agonist-induced analgesia and hypothermia by fluoxetine.

The effect of fluoxetine, a selective 5-HT reuptake inhibitor on the analgesic and hypothermic response of trans-(+/-)-3,4-dichloro-N-methyl-N-2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methane sulphonate (U-50,488H) and (+/-)-trans-N-methyl-N-2-(1-pyrrolidinyl)-cyclohexyl] benzob] thiophene-4-acetamide (PD 117302), kappa-opioid receptor agonists, was determined in female Sprague-Dawley rats using the tail-flick method and telethermometer, respectively. Intraperitoneal injections of U-50,488H (U50) and PD 117302 (PD117) produced a dose-dependent analgesic and hypothermic response. Fluoxetine (10 mg/kg, i.p.) by itself did not produce an analgesic response. The analgesic response to U50 (10, 20, and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine injected intraperitoneally 60 min prior to the injection of kappa-opioid agonists. Similarly, the hypothermic response of U50 (20 and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine. The results indicate that selective kappa-opioid receptor agonists-induced analgesia and hypothermia is potentiated by fluoxetine, suggesting the role of extracellular 5-HT in the kappa-opioid receptor-mediated analgesia and hypothermia.