Intracerebroventricular injection of trazodone produces 5-HT receptor subtype mediated anti-nociception at the supraspinal and spinal levels

Serotonin (5-HT) mediated anti-nociceptive effects induced by an anti-depressant, trazodone, are related to 5-HT1A receptor activities at the supraspinal level. 5-HT3 receptor activation via the descending anti-nociceptive pathways may contribute to the trazodone mediated anti-nociception at the spinal level. Intracerebroventricular (i.c.v.) injection of trazodone dose-dependently impaired nociceptive responses in the formalin test in mice. Six and 15 mug of trazodone inhibited the early (P < 0.05 or 0.01) and the late phases of the formalin test (P < 0.05 or 0.01), while 3 mug had no effect. We examined the effects of a selective 5-HT1A receptor antagonist, WAY-100635, a single injection of which induced hyperalgesia (P < 0.05), and blocked the anti-nociceptive effects of trazodone (P < 0.01) when the two were simultaneously injected i.c.v. Intrathecal (i.t.) injection of a selective 5-HT3 receptor antagonist, 3-tropanylindole-3-carboxylate hydrochloride, blocked the anti-nociceptive effects of i.c.v. trazodone (P < 0.01), while WAY-100635 (i.t.) did not impair trazodone mediated anti-nociception. Trazodone mediated anti-nocicepton is related to serotonergic activity at both the supraspinal and the spinal level. (C) 2004 Elsevier B.V. and ECNP. All rights reserved.