LONG-TERM ETHANOL ADMINISTRATION METHODS FOR RATS - ADVANTAGES OF INHALATION OVER INTUBATION OR LIQUID DIETS

An administration paradigm based on ethanol vaporization in multiple air-tight chambers has been developed to examine the biological effects of chronic exposure to ethanol. Sprague/2-Dawley rats, without surgical or pharmacological intervention, maintain normal growth curves and 175 ± 7 mg/dl blood ethanol levels for more than 2 weeks of continuous ethanol exposure. In the initial 48 hr, low ethanol vapor concentrations (22 mg/liter) accustom the subjects to breathing ethanol. On Day 3, vapor concentrations are raised to 25 mg/liter. Depending upon their blood ethanol levels on Day 5, rats are moved to chambers at one of three concentrations (23,25, or 27 mg/liter) so as to equalize their subsequent levels: rats with Day 5 blood levels between 120 and 220 mg/dl remain in a chamber at 25 mg/liter, those below 120 mg/dl are exposed to 27 mg/liter, while those above 220 mg/dl are exposed to 23 mg/liter. Blood ethanol is remeasured and similar adjustments are made every 2 days for the next 2 weeks. On termination of treatment, subjects exhibit ethanol tolerance (as measured by hypothermic response to a challenge dose of ethanol) and dependence (as measured by open-field behaviors and susceptibility to audiogenic seizures). By supplementing ethanol and control animals' diets with highly palatable foods and salad vegetables, both groups gain weight normally throughout. Our results with this chronic administration method overcome certain limitations experienced with liquid diet and intragastric intubation methods. © 1979 Academic Press, Inc.