Induction of dependence on ethanol by free-choice drinking in alcohol-preferring rats

Studies were performed to examine whether chronic voluntary consumption of ethanol by the selectively-bred, alcohol-preferring P-rats produces physical dependence. Body weight reduction, food restriction and flavoring the 10% ethanol solution increased ethanol consumption from 7 to 14 g ethanol/kg body weight/day when water was freely available. Under similar conditions, consumption by selectively-bred, alcohol-nonpreferring NP-rats increased from 1 to 12 g/kg/day. Removal of ethanol after eight weeks induced physical signs of withdrawal in both lines of animals. In two subsequent studies, P-rats were given food, water and unflavored 10% ethanol ad lib for 15 and 20 weeks; ethanol consumption was 7.2 and 5.6 g/kg/day, respectively. Upon removal of ethanol, manifestations of withdrawal, scored blind in one experiment, developed in 85% of the animals and persisted for 72 hours. Importantly, none in the control groups of P and NP rats given water only exhibited these signs. The ethanol withdrawn groups were hyperactive in both the open-field and the head-poke apparatus. These results indicate that sufficient ethanol was voluntarily consumed by the selectively-bred alcohol-preferring P-rats under free-feeding conditions to produce physical dependence.