The development of metabolic tolerance in the alcohol-preferring P rats: Comparison of forced and free-choice drinking of ethanol

Abstract

Experiments were performed to determine whether metabolic tolerance to alcohol develops in the alcohol-preferring P rats during free-choice drinking. In Experiment 1, alcohol elimination rates (AERs) in female Wistar and P rats were measured as a function of age from 26 to 180 days old. AERs calculated as mmol hr −1 per kg body weight fell with age, whereas AERs expressed as mmol hr −1 per rat increased to reach a constant value after 60 days of age. These data indicate that the chronic effects of ethanol on AER are most easily interpreted if experiments are performed in animals 60 days of age or older and AERs are calculated as mmol hr −1 per rat. In Experiments 2 and 3, P female rats were exposed to alcohol for 6–7 weeks either by free-choice drinking or by forced feeding with liquid diets. With free-choice drinking of alcohol, solid food containig 31 percent of the calories as protein, 10 percent ethanol (v/v) and water were made available ad lib. The liquid diets used for forced ethanol feeding were the Bio-Serv-711 diet, a protein-supplemented Bio-Serv-711 diet and the AIN diet and they contained 18, 32 and 22 percent calories as protein, respectively. When compared with pair-fed or ad lib controls, all the P rats exposed to alcohol by either free-choice or forced-feeding exhibited increased AERs (i.e., metabolic tolerance) after 6–7 weeks. However, if AERs before and after alcohol exposure in the same animals were compared, a net increase in AER was evident only in the P rats on free-choice drinking or forced-fed diets which contained at least 22 percent protein. Alcohol consumption and blood alcohol concentrations of P rats exhibited diurnal variation during free-choice drinking or when they were forced-fed alcohol diets which contained at least 22 percent protein. The high BACs attained in the P rats given the ethanol-containing Bio-Serv-711 diet, presumably because of the lower AERs under this condition, disrupted the diurnal cycling of alcohol ingestion and blood alcohol concentrations. The studies demonstrate that the P rats on chroinic free-choice drinking of alcohol develop metabolic tolerance to much the same degree as animals forced fed ethanol contained in liquid diets. Additionally, they demonstrate that, in animals fed ethanol-containing liquid diets, a net increase in AER after alcohol exposure is evident only if dietary protein constitutes at least 22 percent of the total calories.