5-HT1A agonists induce central cholinergic antinociception.

The antinociceptive effects of the 5-HT1A agonists buspirone [3 mg/kg intraperitoneally (i.p.)], gepirone (3-6 mg/kg i.p.), and 8-OH-DPAT [3-5 mg/kg i.p.; 1-3 micrograms per mouse intracerebroventricularly (i.c.v.)] 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 atropine (5 mg/kg i.p.), the ACh depletor hemicholinium-3 (1 microgram per mouse i.c.v.), and the 5-HT1A antagonist NAN 190 (0.5 microgram per mouse i.c.v.), but not by naloxone (1 mg/kg i.p.), the GABAB antagonist CGP 35348 (100 mg/kg i.p.), and pertussis toxin (0.25 microgram per mouse i.c.v.). 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 5HT1A 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.