McCool Brian A, Chappell Ann M
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Alcohol. 2015 Mar;49(2):111-20. doi: 10.1016/j.alcohol.2015.01.003. Epub 2015 Jan 21.
Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent 'high' and 'low' drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption.
近交系小鼠品系为理解控制乙醇导向行为和神经生物学的遗传机制提供了重要契机。它们已被专门用于了解导致乙醇消耗、急性中毒以及对慢性影响敏感性的细胞机制。然而，一些品系的乙醇消耗量有限，限制了我们对诸如与依赖相关的乙醇摄入量等临床相关终点的理解。此前使用味精（MSG或鲜味）的新型味觉替代程序的研究表明，该程序可极大地提高使用其他方法表现出有限饮酒表型的小鼠品系的乙醇消耗量。在当前研究中，我们采用这种味精替代程序来研究通过被动蒸汽吸入诱导产生的乙醇依赖如何改变C57BL/6J和DBA/2J小鼠的乙醇饮用量。这些品系分别代表“高”和“低”饮酒表型。我们发现，味精替代极大地促进了两个品系的乙醇饮用，同样，无论品系如何，乙醇依赖都会增加乙醇消耗量。然而，DBA/2J小鼠对依赖增强的饮酒表现出更高的敏感性，这表现为针对较低乙醇浓度的饮用行为以及相对于基线摄入量水平的情况。DBA/2J小鼠还表现出与戒断相关的焦虑样行为，而C57BL/6J小鼠则没有。这些发现表明，味精替代程序可用于研究一系列饮酒表型中依赖增强的乙醇消耗情况，并且C57BL/6J和DBA/2J小鼠可能代表了产生依赖增强的乙醇消耗的独特神经行为途径。
