5-HT1A agonists induce central cholinergic antinociception

The antinociceptive effects of the 5-HT1A agonists buspirone [3 mg/kg intraperitoneally (IP)], gepirone (3-6 mg/kg IF), and 8-OH-DPAT [3-5 mg/kg IF; 1-3 mu g per mouse intracerebroventricularly (ICV)] were examined in mice by using the hot plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Buspirone, gepirone, and 8-OH-DPAT produced significant antinociception, which was prevented by at ropine (5 mg/kg IF), the ACh depletor hemicholinium-3 (1 mu g per mouse ICV), and the 5-HT1A antagonist NAN 190 (0.5 mu g per mouse ICV), but not by naloxone (1 mg/kg IF), the GABAB antagonist CGP 35348 (100 mg/kg IF), and pertussis toxin (0.25 mu g per mouse ICV). NAN 190, which totally antagonized buspirone, gepirone, and 8-OH-DPAT antinociception, did not modify the analgesic effect of morphine (5 mg/kg subcutaneously). In the antinociceptive dose range, none of the 5HT(1A) agonists impaired mouse performance evaluated by rota-rod and hole board tests. On the basis of these data, it can be postulated that buspirone, gepirone, and 8-OH-DPAT exert an antinociceptive effect mediated by a central amplification of cholinergic transmission. (C) 1997 Elsevier Science Inc.