5-Hydroxytryptamine sub(3) receptor antagonism modulates a noxious visceral pseudoaffective reflex

• Published in: Neuropharmacology 1995-01, Vol.34 (3), p.263-267
• Main Authors: Banner, SE, Carter, M, Sanger, G J
• Format: Article
• Language: English
• ISSN: 0028-3908

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 colo-rectal distension in the anaesthetized rat. Methiothepin (100 mu g/kg) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 mu g/kg) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 mu g/kg, causing a 57.5 plus or minus 0.9% reduction. An ID sub(50) value of 36.7 mu g/kg was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID sub(50) of 0.4 mu g/kg. 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 colo-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-phenyl-biguanide. However, 8-OH DPAT (100 mu g/kg) facilitated pressor responses.