INFLUENCE OF 5-HT3 RECEPTOR ANTAGONISTS IN VISCEROMOTOR AND NOCICEPTIVE RESPONSES TO RECTAL DISTENSION BEFORE AND DURING EXPERIMENTAL COLITIS IN RATS

We investigated the possible involvement of 5-HT3 receptors in the col onic motor alterations and abdominal pain evoked by rectal distension (RD) in rats, under normal and inflammatory conditions. Responses to R D were evaluated by electromyography in rats treated with 5-HT3 antago nists (ondansetron and cilansetron, 0.1 and 1 mg/kg, intraperitoneally ), before and 3 days after intarectal administration of TNB/ethanol. R D evoked a significant (P < 0.05) and gradual inhibition of the occurr ence of colonic spike bursts (SE) and a gradual increase in abdominal SE from 11 mm in diameter on wards. Ondansetron and cilansetron (0.1 m g/kg) significantly reduced both the colonic (62 and 66%, respectively ) and the abdominal response (28 and 61%, respectively) for an 11 mm d iameter of RD. After TNB/ethanol, both colonic and abdominal responses to RD were significantly (P < 0.05) enhanced and appeared for a lower diameter (9 mm) (colon: 4.8 +/- 0.9 vs 8.4 +/- 1.1, abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4). Cilansetron (0.1, 1 mg/kg) significantly (P < 0.0 5) attenuated the TNB-induced colonic motor inhibition, while ondanset ron and cilansetron (0.1, 1 mg/kg) reduced the TNB-induced increase in abdominal response. We conclude that 5-HT and 5-HT3 receptors mediate RD-induced viscerosensitive alterations in rats, both in normal condi tions and during TNB-induced rectocolitis. However, the relative effic acy of the 5-HT3 receptor antagonists depends on the experimental cond itions (intact or inflamed bowel) and does not appear to increase with the dose.