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

Abstract

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] benzo[ b] thiophene-4-acetamide (PD 117302), κ-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, ip) by itself did not produce an analgesic response. The analgesic response to U50 (10, 20, and 40 mg/kg, ip) and PD117 (7.5, 15, and 22.5 mg/kg, ip) was potentiated by fluoxetine injected intraperitoneally 60 min prior to the injection of κ-opioid agonists. Similarly, the hypothermic response of U50 (20 and 40 mg/kg, ip) and PD117 (7.5, 15, and 22.5 mg/kg, ip) was potentiated by fluoxetine. The results indicate that selective κ-opioid receptor agonists-induced analgesia and hypothermia is potentiated by fluoxetine, suggesting the role of extracellular 5-HT in the κ-opioid receptor-mediated analgesia and hypothermia.