McCool Brian A, Chappell Ann M
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157 USA.
Alcohol. 2014 Feb;48(1):55-61. doi: 10.1016/j.alcohol.2013.10.008. Epub 2013 Nov 22.
Inbred mouse strains such as C57BL/6J (B6) and DBA/2J (D2) and related strains have been used extensively to help identify genetic controls for a number of ethanol-related behaviors, including acute intoxication and sensitivity to repeated exposures. The disparate ethanol drinking behaviors of B6 mice expressing high-drinking/preference and D2 mice expressing low-drinking/preference have yielded considerable insight into the heritable control of alcohol drinking. However, the B6-high and D2-low drinking phenotypes are contrasted with ethanol-conditioned reward-like behaviors, which are robustly expressed by D2 mice and considerably less expressed by B6 mice. This suggests that peripheral factors, chiefly ethanol taste, may help drive ethanol drinking by these and related strains, which complicates mouse genetic studies designed to understand the relationships between reward-related behaviors and ethanol drinking. Traditional approaches such as the sucrose/saccharin-substitution procedure that normally accentuate ethanol drinking in rodents have had limited success in low drinking/preferring mice such as the D2 line. This may be due to allelic variations of the sweet taste receptor subunit, expressed by many ethanol low-drinking/preferring strains, which would limit the utility of these types of substitution approaches. We have recently shown (McCool & Chappell, 2012) that monosodium glutamate (MSG), the primary component of umami taste, can be used in a substitution procedure to initiate ethanol drinking in both B6 and D2 mice that greatly surpasses that initiated by a more traditional sucrose-substitution procedure. In this study, we show that ethanol drinking initiated by MSG substitution in D2 mice, but not sucrose substitution, can persist for several weeks following removal of the flavor. These findings further illustrate the utility of MSG substitution to initiate ethanol drinking in distinct mouse strains.
近交系小鼠品系，如C57BL/6J（B6）和DBA/2J（D2）及相关品系，已被广泛用于帮助确定多种与乙醇相关行为的遗传控制因素，包括急性中毒和对重复暴露的敏感性。表达高饮酒量/偏好的B6小鼠和表达低饮酒量/偏好的D2小鼠在乙醇饮用行为上的差异，为酒精饮用的遗传控制提供了相当多的见解。然而，B6高饮酒和D2低饮酒表型与乙醇条件性奖赏样行为形成对比，D2小鼠能强烈表达这种行为，而B6小鼠表达程度则低得多。这表明外周因素，主要是乙醇味道，可能有助于驱动这些及相关品系的小鼠饮用乙醇，这使得旨在理解奖赏相关行为与乙醇饮用之间关系的小鼠遗传学研究变得复杂。传统方法，如通常能增强啮齿动物乙醇饮用的蔗糖/糖精替代程序，在低饮酒/偏好小鼠（如D2品系）中取得的成功有限。这可能是由于许多低饮酒/偏好乙醇的品系所表达的甜味受体亚基的等位基因变异，这将限制这类替代方法的效用。我们最近发现（麦库尔和查佩尔，2012年），鲜味的主要成分谷氨酸钠（MSG）可用于替代程序，在B6和D2小鼠中引发乙醇饮用，其效果大大超过更传统的蔗糖替代程序。在本研究中，我们表明，D2小鼠中由MSG替代而非蔗糖替代引发的乙醇饮用，在去除味道后可持续数周。这些发现进一步说明了MSG替代在不同小鼠品系中引发乙醇饮用的效用。
