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

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 containing 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.(ABSTRACT TRUNCATED AT 250 WORDS)