ArticleSerotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in ratsBardin, Laurent; Lavarenne, Jeannine; Eschalier, Alain* Author Information INSERM EGG04, Laboratoire de Pharmacologie Médicale, Faculté de Médecine, 63001 Clermont-Ferrand Cedex, France *Corresponding author. Tel.: +33-4-7360-8030; fax: +33-4-7327-7162 E-mail: [email protected] Received 9 February 1999; received in revised form 13 October 1999; accepted 30 November 1999. Pain: May 2000 - Volume 86 - Issue 1 - p 11-18 doi: 10.1016/S0304-3959(99)00307-3 Buy Metrics Abstract The present study was designed to investigate which subtypes of spinal 5-HT receptors are involved in 5-HT-induced antinociception using the mechanical pain test. Serotonin and various selective antagonists or agonists for 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3 and 5-HT4) were administered intrathecally (i.t.) in rats. The i.t. injection of 5-HT (1 μg) produced significant antinociceptive effects using the paw pressure test. Pretreatment with the 5-HT2C receptor antagonist mesulergine (1 and 10 μg) and the 5-HT3 receptor antagonist tropisetron (1 and 10 μg) reversed totally the antinociception induced by 5-HT. Furthermore, at a dose of 10 μg, both the 5-HT2A receptor antagonist ketanserin and the 5-HT1B receptor antagonist penbutolol, but neither the 5-HT1A receptor antagonist WAY 100635 nor the 5-HT4 receptor antagonist GR113808, attenuated the antinociceptive effect induced by 5-HT. In addition, an i.t. injection of the 5-HT3 agonist mCPBG induced significant antinociceptive effects whereas the 5-HT2 agonist DOI did not produce analgesia. These results suggest that although the precise degree of the involvement of spinal serotonergic 5-HT3 receptors remains to be elucidated due to some differences in the effect of agonists or antagonists, these receptors seem to play a role in the antinociceptive effect of 5-HT against a mechanical acute noxious stimulus. The involvement of 5-HT2C is more questionable due to the observed discrepancies between the effects of the used agonist and antagonist. 5-HT1A and 5-HT4 receptors do not seem to be involved. In addition, a possible functional interaction between spinal serotonergic receptors may exist. © 2000 Lippincott Williams & Wilkins, Inc.