Radcliffe R A, Erwin V G, Wehner J M
Institute for Behavioral Genetics, University of Colorado, Boulder 80303-0447, USA.
Alcohol Clin Exp Res. 1998 Nov;22(8):1673-9.
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 (LAFT) 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.
据推测，对酒精的耐受性涉及某种形式的神经元可塑性，这种可塑性与介导学习和记忆的可塑性相似或相同。为了进一步研究这种可能性，我们检验了以下假设：对酒精的急性功能性耐受性（AFT）与巴甫洛夫式学习任务——恐惧条件反射在基因上相关。对因获得AFT能力不同而进行选择性培育的小鼠进行恐惧条件反射测试。实验对象接受与宽带点击器配对的轻度足部电击，并在24小时后测试它们对条件反射箱（环境）、改变后的箱子以及点击器的僵住反应。结果发现，选择用于高AFT（HAFT）的原始品系和复制品系在对环境和点击器的反应中僵住的程度明显高于选择用于低AFT（LAFT）的品系。在第二个实验中，首先对源自C57BL/6（B6）和DBA/2（D2）小鼠品系的F2群体进行恐惧条件反射测试，3周后进行AFT测试。AFT被定义为在给予1.75 g/kg乙醇后首次在圆棒上恢复平衡时以及随后给予2.0 g/kg剂量后测定的血液酒精水平之间的差异。与HAFT和LAFT的结果一致，在F2小鼠中，发现对环境的僵住反应与AFT显著正相关（r = 0.38，p = 0.04）。结果表明，恐惧条件反射和AFT的共同变化可能由一个或多个相同或至少紧密连锁的基因介导。对这种相关性的进一步剖析可能揭示AFT和恐惧条件反射共有的神经元机制。
