The intravenous (i.v.) administration of serotonin (5-HT) to lightly pentobarbital-anesthetized rats is known to produce a triad of reflex cardiovascular responses, distinct afferent-mediated pseudaffective reactions, and a vagally mediated inhibition of the nociceptive tail-flick (TF) reflex consistent with 5-HT acting as a noxious stimulus. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating these responses. Lightly pentobarbital-anesthetized 16-week-old male Sprague-Dawley rats which had been treated as neonates (in the first 48 h of life) with capsaicin (50 micrograms/kg, s.c.) were compared to age-matched neonatal vehicle-treated controls. Whereas the i.v. administration of 5-HT produced a dose-dependent (6-96 micrograms/kg, i.v.) inhibition of the nociceptive TF reflex (ED50 = 48.1 +/- 11.3 micrograms/kg; n = 7) and distinct pseudaffective responses (usually by 24-48 micrograms/kg) in vehicle-treated rats, 5-HT (6-192 micrograms/kg, i.v.) failed to significantly alter TF latency or produce pseudaffective behaviors in the capsaicin-treated rats (n = 10). There was no difference in baseline TF latencies between the two groups. There were essentially no differences between vehicle- and capsaicin-treated rats with respect to the initial cardiopulmonary vagal afferent-mediated (Bezold-Jarisch reflex) decreases in heart rate and arterial blood pressure or the subsequent pressor phase. However, the magnitude of the late hypotensive phase was significantly greater in capsaicin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)