Withdrawal syndrome following subchronic treatment with anxiolytic agents

The acute administration of diazepam (0.1-2.5 mg/kg IP), sulpiride (0.5-20 mg/kg IP) and tiapride (0.5-40 mg/kg IP) to the mouse enhanced exploratory activity (rearings/line crossings) in the brightly illuminated white area of a two compartment white/black anxiety test box, with a corresponding decrease in the black, indicating an anxiolytic action. This profile of change was maintained during a twice daily administration for 7 days with diazepam (2.5 and 10 mg/kg), sulpiride (5 and 20 mg/kg) and tiapride (10 and 40 mg/kg). However, 8 and 48 hr following withdrawal of diazepam, the profile of exploratory behaviour was reversed to a preference for the black area: by 96 hr values for behaviour had returned to control levels. In contrast, an anxiolytic profile of action was maintained 8 and 48 hr following the withdrawal of sulpiride and tiapride, the values returning to control levels after 96 hr. It is concluded that a sub-chronic treatment with diazepam, sulpiride and tiapride induces an anxiolytic profile of action in the mouse model, that an anxiogenic profile follows the abrupt withdrawal of diazepam but that this is not recorded following the abrupt withdrawal of sulpiride and tiapride.