Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats

Abstract

Serotonergic systems are involved in the central regulation of nociceptive sensitivity. Fluoxetine, a selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT), was administered orally (0.16, 0.32, 0.8 mg kg−1 daily for 7 days), intraperitoneally (0.04, 0.08, 0.16 mg kg−1 day−1 for 7 days and a single dose of 0.32 mg kg−1) and intracerebroventricularly(10 μg/rat) to rats and nociceptive sensitivity was evaluated using the formalin test (50 μL of 2.5% formalin injected subcutaneously). The effect of fluoxetine was also studied in the presence of 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) and after co-administration with morphine. Oral (0.8 mg kg−1), intraperitoneal (0.16 and 0.32 mg kg−1) and intracerebroventricular (10 μg/rat) fluoxetine induced antinociception in the late phase of the formalin test. Furthermore, intrathecal administration of 5-HT (100 μg/rat) induced an analgesic effect. The analgesic effect of fluoxetine (0.16 and 0.32 mg kg−1, i.p.) and 5-HT (100 μg/rat, i.t.) was abolished by pre-treatment with 5,7-DHT (100 μg/rat, i.t.). In addition, the analgesic effect of 5-HT (100 μg/rat, i.t.) was decreased by pre-treatment with naloxone(2 mg kg−1, i.p.). Morphine (5 mg kg−1, i.p.) induced analgesia that was increased by fluoxetine (0.32 mg kg−1, i.p.). These results suggest that fluoxetine has an antinociceptive effect in tonic inflammatory pain through functional alteration of the serotonergic system and also potentiates the analgesic effect of morphine.