Differential involvement of central 5-HT1B and 5-HT3 receptor subtypes in the antinociceptive effect of paracetamol

Objective: We investigated the effect of pre-treatment with ondansetron or CP 93129 (a 5-HT1B agonist) on the antinociceptive activity of paracetamol and the changes in central 5-HT3 receptors induced by paracetamol alone or co-administered with ondansetron. Materials and Subjects: Male Wistar rats (eight per group) were injected with ondansetron (2 and 4 mg/kg s. c.) or CP 93 129 (0.5, 1 and 2 mg/kg s. c.) 15 min before paracetamol (400 mg/kg, i.p.). Methods: Pain threshold was evaluated in the hot-plate or in the paw pressure test 30 min after the last treatment. 5-HT3 receptor binding capacity was measured in the frontal cortex, temporal-parietal cortex and midbrain by means of radioligand binding technique. Statistical analysis was done using ANOVA followed by Student-Newman-Keuls test and 2 X 2 factorial analysis when appropriate. Results: Pre-treatment with ondansetron, at doses of 2 and 4 mg/kg, did not affect the antinociceptive activity of paracetamol in the hot-plate test and in the paw pressure test. Paracetamol did not change the characteristics of 5-HT3 receptors in all the areas investigated. Ondansetron (4 mg/kg s. c) per se significantly increased the 5-HT3 receptor number in the areas used, the effect not being modified by co-administration with paracetamol. On the other hand, CP 93129 (2 mg/kg s. c.) significantly prevented the effect of paracetamol in both algesimetric tests used. Conclusions: Our data indicate that 5-HT1B but not 5-HT3 receptors are involved in the antinociceptive effect of paracetamol in our experimental conditions.