Grisel Judith E, Beasley John B, Bertram Emma C, Decker Brooke E, Duan Chunyu A, Etuma Mahder, Hand Annie, Locklear Mallory N, Whitmire Matthew P
Psychology, Bucknell University Lewisburg, PA, USA.
Neuroscience, Furman University Greenville, SC, USA.
Front Neurosci. 2014 Nov 4;8:345. doi: 10.3389/fnins.2014.00345. eCollection 2014.
Most adults consume alcohol with relative impunity, but about 10-20% of users persist (or progress) in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug's reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5 g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction.
大多数成年人饮酒相对无害，但约10%-20%的饮酒者尽管面临越来越多严重后果，仍持续（或增加）饮酒量。因此，在与长期饮酒相关的神经适应性变化根深蒂固之前识别出高危个体，是减轻和预防终末期疾病及其毁灭性影响的关键一步。部分由于缺乏评估对药物强化特性初始敏感性的动物模型，解释饮酒易感性受到了阻碍，而这种初始敏感性是过度饮酒发展过程中的一个重要内表型。在此，我们在条件性位置偏爱范式的一种新应用中评估了药物的初始奖赏效应。与之前所有采用重复给药的研究不同，我们在三个品系的雄性和雌性受试者中均证明，他们对与单次给予1.5 g/kg乙醇配对的环境表现出强烈偏爱。该模型验证了一种对酒精主观奖赏效应初始敏感性的检测方法，酒精是一种对大脑和社会都有多种影响的广泛使用的药物，并为理解和治疗成瘾的理论驱动的内表型药物遗传学方法提供了一种新工具。
