School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
College of Chemical Engineering, Changchun University of Technology, Changchun, China.
Neuropharmacology. 2021 Mar 15;186:108446. doi: 10.1016/j.neuropharm.2020.108446. Epub 2021 Jan 18.
For several decades, genetically selected alcohol-preferring rats have been successfully used to mimic and study alcohol use disorders (AUD). These rat lines have been instrumental in advancing our understanding of the neurobiology of alcoholism and enabling pharmacological studies to evaluate drug efficacy on alcohol drinking and relapse. Moreover, the results of these studies have identified genetic variables that are linked to AUD vulnerability. This is an up-to-date review that focuses on genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. To support the translational relevance of the findings that are obtained from msP rats and highlight important similarities to AUD patients, we also discuss the results of recent brain imaging studies. Finally, to demonstrate the importance of studying sex differences in animal models of AUD, we present original data that highlight behavioral differences in the response to alcohol in male and female rats. Female msP rats exhibited higher alcohol consumption compared with males. Furthermore, msP rats of both sexes exhibit higher anxiety- and depressive-like behaviors in the elevated plus maze and forced swim test, respectively, compared with unselected Wistar controls. Notably, voluntary alcohol drinking decreases foot-shock stress and depressive-like behavior in both sexes, whereas anxiety-like behavior in the elevated plus maze is attenuated only in males. These findings suggest that male and female msP rats both drink high amounts of alcohol to self-medicate negative affective symptoms. For females, this behavior may be driven by an attempt to treat stress and depressive-like conditions. For males, generalized anxiety appears to be an important additional factor in the motivation to drink alcohol. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'
几十年来，经过基因选择的酒精偏好大鼠已成功用于模拟和研究酒精使用障碍（AUD）。这些大鼠品系对于推进我们对酒精中毒的神经生物学的理解以及进行评估药物对饮酒和复发的疗效的药理学研究具有重要作用。此外，这些研究的结果确定了与 AUD 易感性相关的遗传变量。这是一篇最新的综述，重点介绍了经过基因选择的 Marchigian Sardinian 酒精偏好（msP）大鼠。为了支持从 msP 大鼠获得的发现的转化相关性，并强调与 AUD 患者的重要相似性，我们还讨论了最近的脑成像研究结果。最后，为了证明在 AUD 动物模型中研究性别差异的重要性，我们提供了原始数据，突出了雄性和雌性大鼠对酒精的反应中的行为差异。与雄性相比，雌性 msP 大鼠的酒精摄入量更高。此外，与未经选择的 Wistar 对照相比，雄性和雌性 msP 大鼠在高架十字迷宫和强迫游泳试验中分别表现出更高的焦虑和抑郁样行为。值得注意的是，自愿饮酒可降低两性大鼠的足底电击应激和抑郁样行为，而高架十字迷宫中的焦虑样行为仅在雄性中减轻。这些发现表明，雄性和雌性 msP 大鼠都大量饮酒以自我治疗消极的情感症状。对于女性，这种行为可能是为了治疗压力和抑郁样状况。对于男性，普遍的焦虑似乎是饮酒动机的一个重要附加因素。本文是关于“滥用物质的易感性”特刊的一部分。
