Genetic correlation of ethanol-induced ataxia and cerebellar Purkinje neuron depression among inbred strains and selected lines of rats.

In the present study, we compared phenotypic differences in behavioral and neurophysiological responses to acute ethanol administration among six inbred rat strains. Genetic variation was found both for ataxia, as measured by loss of righting response (sleep time) after a hypnotic dose of ethanol, and for the depressant action of ethanol on the spontaneous discharge of cerebellar Purkinje neurons. Results from an analysis of covariance of these phenotypes, measured among the inbred strains, provided strong evidence for a high genetic correlation between sleep time and inhibition of cerebellar Purkinje neuron discharge in response to acute ethanol administration. However, ethanol metabolism was also found to correlate with the behavioral sensitivity of rats to ethanol. Preliminary data from the third generation of replicate lines of rats currently being selectively bred for high and low acute sensitivity to ethanol shows a trend toward divergence of both ethanol sleep time and neuronal sensitivity to acute ethanol. The conclusion from these data supports the hypothesis that the cerebellum is an important locus of ethanol action, and suggests that neuronal sensitivity to ethanol will continue to diverge between these rat lines as selection for the sleep time phenotype progresses.