Barbiturate physical dependence in mice: effects of neuroleptics and diazepam on the withdrawal syndrome

Diazepam (8 mg/kg) quickly and effectively reduced the incidence of withdrawal symptoms in phenobarbital dependent C57BL/6J male mice. In contrast, the neuroleptic agents employed (chlorpormazine, haloperidol, or reserpine) or alpha-methyl-p-tyrosine tended to exacerbate the withdrawal syndrome. Chlorpromazine and haloperidol were approximately equally potent in their effects; this would suggest that their antidopaminergic effects were not the primary mechanism of action for the increased incidence of withdrawal symptoms.