Control of ethanol withdrawal symptoms in mice by phenytoin

Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.