ACUTE FUNCTIONAL TOLERANCE TO ETHANOL AND FEAR CONDITIONING ARE GENETICALLY CORRELATED IN MICE

It has been speculated that tolerance to alcohol involves some form of neuronal plasticity that is similar to or the same as that mediating learning and memory. To investigate this possibility further, we teste d the hypothesis that acute functional tolerance (AFT) to alcohol is g enetically correlated to a Pavlovian learning task: fear conditioning. Mice selectively bred for differences in ability to acquire AFT were tested for fear conditioning. Subjects received a mild footshock paire d to a broadband clicker and were tested 24 hr later for their freezin g response to the conditioning chamber (context), to an altered chambe r, and to the clicker. Both the original and replicate lines selected for high AFT (HAFT) were found to freeze significantly more than those selected for low AFT (LAFT) in response to the context and to the cli cker. In a second experiment, an F-2 population derived from the C57BL /6 (B6) end DBA/2 (D2) mouse strains were tested first for fear condit ioning, followed 3 weeks later by AFT testing. AFT was defined as the difference between blood alcohol levels determined at the time of rega in balance on a dowel rod first after 1.75 g/kg of ethanol and again a fter a subsequent dose of 2.0 g/kg. Consistent with results from HAFT and LAFT, freezing to context was found to be significantly positively correlated to AFT (r = 0.38, p = 0.04) in the F-2 mice. The results s uggest that co-variation in fear conditioning and AFT may be mediated by one or more of the same or at least tightly linked genes. Further d issection of this correlation may reveal neuronal mechanisms common to both AFT and fear conditioning.