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Objectives: Evaluate antinociceptive activity of fluoxetine and the interaction of fluoxetine with naloxone and ondansetron. Methods: 32 albino mice of either sex were divided into 4 groups of 8 mice each: group I received normal saline, group II received fluoxetine; group III received fluoxetine + naloxone; group IV received  fluoxetine + ondansetron. Fluoxetine and naloxone were given subcutaneously whereas ondansetron was given intraperitoneally. Eddy’s hot plate analgesiometer was used. Latency of licking of paw or jumping from the hot plate was recorded at intervals  after giving study drugs in each group. Results: Fluoxetine produced a significant increase in the latency of licking of paw or jumping as compared to control at all time intervals except at 120 minutes with onset of antinociceptive effect within 30 min (p<0.01) and maximum effect at 60 min time interval  (p<0.001). There was no significant difference between the control group and the fluoxetine + naloxone or fluoxetine + ondansetron group at any time point. Pre-treatment with naloxone and ondansetron antagonized the antinociceptive effects of fluoxetine. Conclusion: Administration of naloxone and ondansetron in fluoxetine treated mice antagonized the antinociceptive activity of fluoxetine. Therefore, antinociceptive activity of fluoxetine may be mediated through µ-opiod and 5HT3 receptors. Keywords: anti-nociceptive, Eddy’s hot plate, fluoxetine, naloxone, ondansetron.

EXPERIMENTAL STUDY TO EVALUATE THE ANTINOCICEPTIVE ACTIVITY OF FLUOXETINE AND ITS INTERACTION WITH NALOXONE AND ONDENSETRON IN MICE