Induction of physical dependence in rats by ethanol inhalation without the use of pyrazole

Abstract

Rats were exposed to increasing air ethanol concentrations (14 to 28 mg/liter) over a 10-day period without the use of pyrazole. There was a positive correlation between the rising air ethanol concentrations in the chamber and the concentrations of ethanol in the blood. On Day 10 the animals were removed from the chamber with a mean blood ethanol concentration of 3.13 mg/ml and observed for signs of withdrawal over a 24-hr period. During this time all animals manifested spontaneous signs of withdrawal and convulsions on handling. There was a positive correlation between the spontaneous signs and convulsions on handling. The disappearance of ethanol from the blood followed zero-order kinetics over the first 7 hr. In the withdrawal phase of the experiments a definite negative correlation existed between the decreasing blood ethanol concentrations and the rise in the scores for convulsions on handling. This inhalation procedure is a simple, reproducible approach for causing physical dependence on ethanol in rats without the use of pyrazole and with the maintenance of original body weight.