Alcohol dependence and withdrawal in the rat. An effective means of induction and assessment

Numerous problems have been associated with previous attempts to develop a suitable method for the induction and assessment of alcohol dependence and withdrawal syndrome in the rat. Using our modification of a common inhalation method for the long-term administration of ethanol, these problems can be eliminated. Adult male rats (Long Evans and Brattleboro) were exposed to ethanol vapor concentrations of 7 to 35 mg/liter of air, which cause rapid development of tolerance and physical dependence. With this inhalation method, it is possible to obtain and easily maintain high levels of ethanol in the blood (150 to 400 mg/dl). When exposure to ethanol is terminated, ethanol is eliminated from the system within 1 to 6 hr. This rapid elimination of ethanol is accompanied by a high susceptibility to withdrawal reactions. The severity of the withdrawal syndrome was assessed within 6 to 24 hr after cessation of the ethanol administration by exposing each rat individually to a 60 to 120-sec period of bell ringing. Convulsive seizures were observed in nearly 90% of the animals tested, with a mortality rate of less than 20%.