The development of chronic tolerance to the motor disrupting effects of ethanol has been studied in genetically heterogeneous rats obtained from the N:NIH stock. The preliminary data demonstrate that the development of tolerance was widely distributed and unimodal in this population of rats. In addition, there was no sex differences in the amount of tolerance developed. Thus, the measure of tolerance chosen and the procedure used to develop tolerance with this population of genetic-heterogeneous rats appears to fulfill the necessary requirements to begin a successful breeding program. Rats from the original gene pool will be selectively breed to form divergent lines of rats based on the degree of functional tolerance obtained after an eight day ethanol exposure period. Three lines of rats will be developed: a line which develops a large amount of functional tolerance to ethanol, a line which develops littler or no functional tolerance to ethanol, and a control line which is randomly mated, irrespective of their tolerance development. Each line will be composed of ten families to minimize rapid inbreeding. It is also proposed that replicates of each trait will theoretically contain all alleles associated with the trait, while alleles not associated with the trait will be randomly distributed. Thus, these animals will be a resource for investigators interested in neurobiological and behavioral correlates of chronic functional tolerance to ethanol.
