Involvement of the serotonergic system in the hypoactive and antinociceptive effects of nicotine in mice.

Pretreatment with the 5-HT2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone did not reduce nicotine-induced hypomotility in mice, nor did MDL 7222, a selective 5-HT3 antagonist. In addition, 8-OH-DPAT and buspirone, 5-HT1A agonists, had no significant effects on nicotine-induced hypomotility. However, 8-OH-DPAT and buspirone did reduce the antinociceptive effects of nicotine in a dose-dependent manner. 8-OH-DPAT blockade of this nicotine effect was reversed by spiperone, a 5-HT1A/2 antagonist. Nicotine's ED50 was increased from 1.00 mg/kg (0.90-1.68) to 2.00 mg/kg (1.6-2.55) and 2.66 (1.7-3.51) by buspirone and 8-OH-DPAT, respectively. Ketanserin, spiperone and MDL 7222 had no significant effect on nicotine-induced antinociception. The present data suggest an important role of 5-HT1A receptors in the modulation of antinociceptive actions of nicotine.