Physical dependence on alcohol in mice.

Although it has not yet been possible to construct a complete model of alcoholism in experimental animals; some aspects of the disease can now be studied with satisfactory laboratory systems. Production of physical dependence requires a period of continuous intoxication; brief intervals of sobriety allow the accrued dependence to disappear. Administration of ethanol by inhalation, with daily injections of pyrazole, allows maintenance of stable blood alcohol levels in mice. In this model, physical dependence arises to its maximum in a week or two and can decay in less than a day. Sedative drugs suppress the mouse withdrawal reactions but drugs that intefere with catecholamine or gamma-aminobutyric acid pathways facilitate withdrawal seizures. Susceptibility to withdrawal seizures is controlled in part by genetic factors.