On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor

Antidepressant drugs are reported to be used as co-analgesics in clinical m anagement of migraine and neuropathic pain. The mechanism through which the y alleviate pain remains unknown. The present study explores the possible m echanism of a selective serotonin reuptake inhibitor (SSR1) fluoxetine-indu ced antinociception in animals. Acetic acid-induced writhing, hot plate and tail-flick test were used to assess fluoxetine-induced antinociception. Fl uoxetine (5-20 mg kg(-1), i.p.) produced a significant and dose-dependent a ntinociceptive effect against acetic acid-induced writhing in mice. Fluoxet ine (20 mg kg(-1)) also exhibited antinociceptive effect in tail flick as w ell as hot plate assays. Further, i.c.v. administration of fluoxetine showe d significant antinociception against writhing test in rats. However, fluox etine (1 mug/10 mul/rat, i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals. Further, pindolol (10 mg kg(-1), i.p.) enha nced fluoxetine-induced antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to blockade by naloxone (5 mg kg(-1), i.p.) and naltrexone (5 mg kg(-1), i.p.). These data suggest that fluoxetine-induced antinociception involves both central opioid and the serotoninergic pathwa ys. (C) 2001 Elsevier Science BY All rights reserved.