Age, strain and anesthetic dependent differences in the nociceptive responses produced by i.v. 5-HT in the rat.

Abstract The intravenous (i.v.) administration of serotonin (5-HT) to rats is a noxious visceral stimulus which produces distinct vagal afferent-mediated pseudaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the tail-flick (TF) reflex and a complex cardiovascular response. In the present study, we examined the effects of age (10 or 16 weeks), strain (Sprague-Dawley, SD; Wistar-Kyoto, WKY; spontaneously hypertensive rats, SHR) and anesthetic (conscious or lightly pentobarbital-anesthetized) on nociceptive (TF reflex and pseudaffective resonses) and cardiovascular responses produced by 5-HT (3–288 μg/kg i.v.). There were no age-related differences in baseline TF latencies in the 3 strains. Further, latencies were generally not significantly different whether rats were tested conscious or lightly anesthetized. There were, however, strain differences. Both conscious or lightly pentobarbital-anesthetized SHR and WKY rats at 10 weeks of agge had significantly faster response latencies than 10 week old SD rats. At 16 weeks of age, only the lightly pentobarbital-anesthetized WKY and SHR showed faster response latencies than SD rats. The WKY and SHR, but not the SD rats, were more sensitive to the nociceptive effect of i.v. 5-HT at 16 weeks of age compared to 10 weeks of age. At both ages, WKY and SHR, but not SD rats, showed an anesthetic-dependent increase in nociceptive sensitivity to i.v. 5-HT. In addition, at both ages regardless of the presence of anesthetic, the order of sensitivity to the nociceptive effects of i.v.5-HT was SD > WKY → SHR. The cardiovascular responses to i.v. 5-HT also were examined at these different strains and in the presence of absence of pentobarbital anesthesia. In general, there were no major differences in the cardiovascular responses to i.v. 5-HT at 10 or 16 weeks of age. The presemce of pentobarbital anesthesia resulted in an increase in the Bezold-Jurisch reflex-mediated hypotension and bradycardia in SD and SHR, but not in WKY, a decrease in the magnitude of the late hypotensive phase in all 3 strains. At all doses of 5-HT tested in lightly anesthetized rats, both the WKY and SHR showed a significantly greater Bezold-Jarisch reflex-mediated hypotension and bradycardia and a less pronounced pressor response compared to SD rats. The magnitude and duration of the late hypottensive phase was similar in SHR and WKY rats, which were greater than SD rats. WKY and SHR showed similar cardiovascular response to i.v. 5-HT except that WKY showed a less pronounced pressor response. In conscious rats, at all doses tested, both the WKY and SHR showed a greater Bezold-Jurisch reflex-mediated hypotension and bradycardia, a less pronounced pressor response and the presence of a late hypotensive phase compared to SD rats. WKY rats showed a greater Bezold-Jurisch reflex-mediated hypotension and bradycardia and a less pronounced pressor response and late hypotensive phase compared to SHR. These results demonstrate that there is a significant influence of strain, age and presence or absencce of pentobarbital anesthetic on the nociceptive actions of i.v. 5-HT and are discussed with respect to strain differences and the developmental aspects of visceral nociception.