Morphine Withdrawal‐induced Diarrhoea and Acetic Acid‐induced Abdominal Constriction: Animal Models for the Evaluation of 5‐HT3 Ligands in the Treatment of Irritable Bowel Syndrome

Abstract

The aim of the study was to evaluate the role of 5-HT3 receptor ligands in animal models of gastric hypermotility and visceral hyperalgesia, symptoms associated with irritable bowel syndrome. The abrupt termination of sub-chronic morphine (in doses of 35, 70, 140 mg kg−1, i.p.) for four days by naloxone (43 mg kg−1 i.p., 3 h after the last morphine injection) results in withdrawal symptoms, of which diarrhoea and jumping behaviour are common in mice. The gastric hypermotility induced by morphine withdrawal is used as an animal model to evaluate 5-HT3 ligands. Acetic acid-induced abdominal constriction in mice serves as a model for visceral hyperalgesia. m-Chlorophenylbiguanide (mCPBG; 2 and 5 mg kg−1, i.p.) and ondansetron (3 and 6 mg kg−1, i.p.), 5-HT3 agonist and antagonist respectively, were used for the study. Ondansetron exhibited a dose-dependent inhibition of diarrhoea and significantly decreased the number of jumps. It also attenuated the abdominal constriction response induced by acetic acid in mice in a dose-dependent manner. mCPBG did not significantly alter diarrhoea or acetic acid-induced abdominal constriction. However mCPBG (5 mg kg−1, i.p) caused a significant increase in number of jumps. The results suggest that 5-HT3 receptor modulators can be used for the treatment of GI dysmotility and associated nociception, and the above models can be used to evaluate 5-HT3 ligands, especially antagonists, in treatment of irritable bowel syndrome.