5-HYDROXYTRYPTAMINE(3) RECEPTOR ANTAGONISM MODULATES A NOXIOUS VISCERAL PSEUDOAFFECTIVE REFLEX

5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed intravenously (i.v.) and studied for their effects on the depressor cardiovascular pseudoaffective reflex evoked by acute noxious cole-rectal distension in the anaesthetized rat. Methiothepin (100 mu g kg(-1)) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 mu g kg(-1)) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 mu g kg(-1), causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7 mu g kg(-1) was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID50 of 0.4 mu g kg(-1). Bell-shaped dose-effect curves were demonstrated for both granisetron and ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar region of the spinal cord prevented the depressor response to cole-rectal distension, suggesting a spinal site of action. The pseudoaffective depressor responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8-OH DPAT, alpha-methyltryptamine or 1-phenylbiguanide. However, 8-OH DPAT (100 mu g kg(-1)) facilitated presser responses. It is suggested that 5-HT3-like receptors may have a role in modulating depressor responses to visceral pain and that in this action different 5-HT3 receptor antagonists are not necessarily equi-effective.