INTRACOLONIC GLYCEROL INDUCES ABDOMINAL CONTRACTIONS IN RATS - ROLE OF 5-HT3 RECEPTORS

Serotonin and 5-HT3 receptors may be involved in the activation of noc iceptive afferent pathways by rectal distension. In rats, intracolonic infusion of glycerol is able to trigger nociceptive inputs as evidenc ed by the occurrence of abdominal constrictions. This work was designe d to evaluate the influence of 5-HT3 receptor antagonists on this refl ex and to approach the site of action by comparing their relative effi cacies according to the route of administration. Male Wistar rats (250 -350 g) were surgically prepared for abdominal electromyography and a catheter was placed in the colonic,lumen. Five days after surgery, ele ctrical activity of abdominal muscles was recorded before and during ( 20 min) intracolonic infusion of glycerol (60% glycerol + 40% saline, rate 0.75 mL/h). Cilansetron was administered intraperitoneally, 15 mi n before glycerol infusion, at doses of 5 to 500 mu g/kg. Granisetron, ondansetron and cilansetron were administred at the dose of 20 mu g/k g by intraperitoneal (ip), intravenous (iv) or intracolonic (ic) route s. The number of abdominal spike bursts was used as an index of viscer al nociception. Intracolonic infusion of glycerol increased significan tly (P < 0.05) the number of abdominal spike bursts during the time of infusion compared with saline (30.6 +/- 6.6 vs 4.5 +/- 3.4 bursts). W hen administered ip, cilansetron dose-dependently reduced the frequenc y of abdominal spike bursts from the dose of 20 mu g/kg ip. Administra tion ip of granisetron and ondansetron at this dose also significantly reduced the number of abdominal spikes (19.0 +/- 6.0 and 18.3 +/- 6.9 respectively). Cilansetron, ondansetron and granisetron were also eff ective by iv and ic routes, cilansetron was more active by the ic rout e. Serotonin, via 5-HT3 receptors, is involved in the mediation of abd ominal contractions induced by intracolonic infusion of glycerol. 5-HT 3 receptor antagonists are also active by ic route suggesting a local site of action. (C) Elsevier, Paris.