Potentiation of physical dependence on diazepam by ondansetron in rats

The effects of ondansetron, a 5-HT3 antagonist, on the development of physical dependence on diazepam were examined in rats using a drug-admixed food method. Rats were treated with diazepam or diazepam in combination with ondansetron for 26 days. After an abrupt withdrawal from diazepam, the incidence of withdrawal signs, such as jerks, tremors and convulsions, and withdrawal scores, were potentiated by co-administration of ondansetron. On the other hand, rats which had been treated with ondansetron alone for 33 days did not show any withdrawal signs after abrupt withdrawal from ondansetron. These findings suggest that ondansetron does not possess physical dependence liability, but does potentiate the development of physical dependence on diazepam. Regulation of serotonergic neurons through 5-HT3 receptors may affect the development of physical dependence on diazepam.