Effects of serotonergic anxiolytics on physical dependence on diazepam in mice

The effects of serotonergic anxiolytics on the development of physical dependence on diazepam were examined in mice. Co-administration of buspirone (5-HT1A agonist) or ondansetron (5-HT3 antagonist), but not mianserin (5-HT1C antagonist) or ketanserin (5-HT2 antagonist) with diazepam potentiated the hypersensitivity to FG 7142 following chronic treatment with diazepam. This potentiation was not ascribable to pharmacokinetic interactions between diazepam and buspirone or ondansetron. These results suggest that co-administration of buspirone or ondansetron with diazepam may potentiate the development of physical dependence on diazepam; 5-HT1A and 5-HT3 receptors may be partially involved in the development of physical dependence on diazepam.