Acute Functional Tolerance to Ethanol and Fear Conditioning Are Genetically Correlated in Mice

Authors

  • Richard A. Radcliffe,

    Corresponding author
    1. Institute for Behavioral Genetics (R.A.R., J.M.W.), University of Colorado, Boulder, Colorado; and the School of Pharmacy (V.G.E., J.M.W.) and the Alcohol Research Center (V.G.E., J.M.W), University of Colorado Health Sciences Center, 4200 East 9rh Avenue, Denver, Colorado 80262
      Reprint requests: Richard A. Radcliffe, Ph.D., Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, CO 80303-0447.
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  • V. Gene Erwin,

    1. Institute for Behavioral Genetics (R.A.R., J.M.W.), University of Colorado, Boulder, Colorado; and the School of Pharmacy (V.G.E., J.M.W.) and the Alcohol Research Center (V.G.E., J.M.W), University of Colorado Health Sciences Center, 4200 East 9rh Avenue, Denver, Colorado 80262
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  • Jeanne M. Wehner

    1. Institute for Behavioral Genetics (R.A.R., J.M.W.), University of Colorado, Boulder, Colorado; and the School of Pharmacy (V.G.E., J.M.W.) and the Alcohol Research Center (V.G.E., J.M.W), University of Colorado Health Sciences Center, 4200 East 9rh Avenue, Denver, Colorado 80262
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  • This work was supported by Grants AA 03527, AA 00141, and HD 07289.

Reprint requests: Richard A. Radcliffe, Ph.D., Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, CO 80303-0447.

Abstract

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 tested the hypothesis that acute functional tolerance (AFT) to alcohol is genetically 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 paired to a broadband clicker and were tested 24 hr later for their freezing response to the conditioning chamber (context), to an altered chamber, 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 (HAFT) in response to the context and to the clicker. In a second experiment, an F2 Population derived from the C57BL/6 (B6) and DBA/2 (D2) mouse strains were tested first for fear conditioning, followed 3 weeks later by AFT testing. AFT was defined as the difference between blood alcohol levels determined at the time of regain balance on a dowel rod first after 1.75 g/kg of ethanol and again after 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 F2 mice. The results suggest 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 dissection of this correlation may reveal neuronal mechanisms common to both AFT and fear conditioning.

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