Study of the antinociceptive activity of fluoxetine and its interaction with morphine and naloxone in mice

OBJECTIVE: To study the probable site of the antinociceptive action of fluoxetine and its interaction with morphine and naloxone.
MATERIAL AND METHODS: The antinociceptive activity of fluoxetine was studied using tail-flick method in the absence and presence of naloxone in mice. Different doses of fluoxetine (2, 5 and 10 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) were administered subcutaneously to select the subanalgesic doses for both. Subanalgesic doses of both the drugs were administered simultaneously to study their interaction on tail-flick latency.
RESULTS: Fluoxetine and morphine produced a dose-dependent antinociceptive action. Combination of the subanalgesic dose of both fluoxetine (2 mg/kg) and morphine (0.5 mg/kg) produced an additive effect. Naloxone in a dose of 1 mg/kg produced a significant (P<0. 001) hyperalgesia at time intervals of 15, 30 and 60 min while in a dose of 2 mg/kg it produced significant (P<0. 001) hyperalgesia at time intervals of 30, 60 and 120 min. Naloxone (2 mg/kg) pretreatment significantly reduced the antinociception produced by fluoxetine.
CONCLUSION: Analgesia produced by fluoxetine may be mediated by ′μ′ opioid receptor, however, mechanisms involving other endogenous opioid peptides could not be ruled out. Fluoxetine as a monotherapy or in combination with other opioids could be useful in the management of pain.