Millie Lauren A, Boehm Stephen L, Grahame Nicholas J
Department of Psychology, Indiana University-Purdue University Indianapolis.
Exp Clin Psychopharmacol. 2020 Aug;28(4):379-387. doi: 10.1037/pha0000359. Epub 2020 Mar 9.
Alcohol consumption may precede, or result from, behavioral inflexibility and contribute to individuals' difficulties ceasing drinking. Attentional set shifting tasks are an animal analog to a human behavioral flexibility task requiring recognition of a previous strategy as inappropriate, and the formation and maintenance of a novel strategy (Floresco, Block, & Tse, 2008). Abstinent individuals with alcohol use disorder, nonalcoholic individuals with a family history of alcoholism, and mice exposed to chronic-intermittent alcohol vapor show impaired behavioral flexibility (Gierski et al., 2013; Hu, Morris, Carrasco, & Kroener, 2015; Oscar-Berman et al., 2009). Behavioral flexibility deficits can be linked to frontal cortical regions connected to the striatum (Ragozzino, 2007), and alterations to the endocannabinoid system, implicated in drug seeking and consumption (Economidou et al., 2006; Serrano & Parsons, 2011), may affect these behaviors. Alcohol-preferring and nonpreferring rodents exhibit differences in CB1 receptor expression (CB1R; Hansson et al., 2007; Hungund & Basavarajappa, 2000), but whether dorsal striatal CB1Rs are important for other alcohol-related behaviors such as attentional set shifting tasks remains unclear. This study assesses whether selectively bred high (HAP) versus low alcohol-preferring mice differ in an operant attentional set shifting task or CB1R levels in the dorsal striatum and whether a history of voluntary alcohol consumption in crossed HAP mice exacerbates inflexibility. Contrary to our hypothesis, neither genetic differences in alcohol preference nor drinking affected set shifting. However, high alcohol-preferring mice-3 mice showed reduced levels of dorsal striatal CB1R compared with low alcohol-preferring-3 mice, suggesting that genetic differences in alcohol consumption may be mediated in part by striatal CB1R. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
饮酒可能先于行为灵活性不足出现，或者是行为灵活性不足的结果，并且会导致个体难以戒酒。注意力转换任务是一种动物版的人类行为灵活性任务，需要识别先前的策略不合适，并形成和维持一种新的策略（弗洛雷斯科、布洛克和谢，2008年）。患有酒精使用障碍的戒酒个体、有酗酒家族史的非酒精个体，以及暴露于慢性间歇性酒精蒸汽的小鼠，都表现出行为灵活性受损（吉尔斯基等人，2013年；胡、莫里斯、卡拉斯科和克罗纳，2015年；奥斯卡-伯曼等人，2009年）。行为灵活性缺陷可能与连接到纹状体的额叶皮质区域有关（拉戈齐诺，2007年），而内源性大麻素系统的改变，与药物寻求和消费有关（埃科诺米杜等人，2006年；塞拉诺和帕森斯，2011年），可能会影响这些行为。偏好酒精和不偏好酒精的啮齿动物在CB1受体表达（CB1R）上存在差异（汉松等人，2007年；洪贡德和巴萨瓦拉贾帕，2000年），但背侧纹状体CB1R对其他与酒精相关的行为（如注意力转换任务）是否重要仍不清楚。本研究评估了选择性培育的高酒精偏好（HAP）小鼠与低酒精偏好小鼠在操作性注意力转换任务或背侧纹状体CB1R水平上是否存在差异，以及杂交HAP小鼠的自愿饮酒史是否会加剧行为灵活性不足。与我们的假设相反，酒精偏好的遗传差异和饮酒都不会影响转换能力。然而，高酒精偏好的小鼠（HAP-3小鼠）与低酒精偏好的小鼠（LAP-3小鼠）相比，背侧纹状体CB1R水平降低，这表明酒精消费的遗传差异可能部分由纹状体CB1R介导。（《心理学文摘数据库记录》（c）2020美国心理学会，保留所有权利）
