Effect of fluoxetine hydrochloride (Lilly 110140), a specific inhibitor of serotonin uptake, on morphine analgesia and the development of tolerance

Fluoxetine, a specific inhibitor of the re-uptake of serotonin in the brain, was found to potentiate the analgesic effect of morphine as measured by the tail-flick method in rats. One dose of fluoxetine thirty minutes prior to analgesic testing in morphine pellet implanted rats was shown to inhibit the analgesic effect of acute challenges of morphine to the same degree as in rats treated daily with fluoxetine during the development of tolerance to morphine. These data indicate that serotonin may play a role in the analgesic effect of morphine, but not in the development of tolerance to narcotic analgesia.