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黑暗中高饮酒量选择小鼠的焦虑样行为及酒精诱导的抗焦虑作用中的基因型和性别差异

Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice.

作者信息

Barkley-Levenson Amanda M, Crabbe John C

机构信息

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; Portland Alcohol Research Center, VA Medical Center, Portland, OR 97239, USA.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; Portland Alcohol Research Center, VA Medical Center, Portland, OR 97239, USA.

出版信息

Alcohol. 2015 Feb;49(1):29-36. doi: 10.1016/j.alcohol.2014.07.022. Epub 2014 Nov 26.

Abstract

Alcohol use disorders and anxiety disorders are highly comorbid in humans. In rodent lines selected for alcohol drinking, differences in anxiety-like behavior are also seen. The High Drinking in the Dark (HDID) lines of mice are selectively bred for drinking to intoxication during limited access to alcohol, and these mice represent a genetic model of risk for binge-like drinking. The present studies investigated whether these selected lines differ from control (HS) mice in basal anxiety behavior or in anxiolytic response to alcohol. We also assessed the genetic correlation between alcohol drinking in the dark (DID) and basal anxiety-like behavior using existing inbred strain data. Mice of both sexes and HDID replicates (HDID-1 and HDID-2) were tested on an elevated zero maze immediately following a DID test. In general, HDID mice showed more time spent in the open arms after drinking alcohol than HS mice, and open-arm time was significantly correlated with blood alcohol concentration. HDID-1 male mice also showed less anxiety-like behavior at baseline (water-drinking controls). In a separate experiment, HDID-1 and HS mice were tested for anxiolytic dose-response to acute alcohol injections. Both genotypes showed increasing time spent in the open arms with increasing alcohol doses, and HDID-1 and female mice had greater open-arm time across all doses. HDID-1 control males showed lower anxiety-like behavior than the HS control males. Inbred strain data analysis also showed no significant genetic relationship between alcohol DID and anxiety. These findings suggest that HDID selection has not produced systematic changes in anxiety-like behavior or sensitivity to alcohol-induced anxiolysis, though there is a tendency in the male mice of the first replicate toward reduced basal anxiety-like behavior. Therefore, anxiety state and sensitivity to alcohol's anxiolytic effects do not appear to contribute significantly to the high drinking behavior of the HDID mice.

摘要

酒精使用障碍和焦虑症在人类中高度共病。在因饮酒而被挑选出的啮齿动物品系中,也观察到了焦虑样行为的差异。黑暗中高饮酒量(HDID)品系的小鼠是在有限的酒精获取期间被选择性培育至醉酒状态的,这些小鼠代表了类似暴饮的饮酒风险的遗传模型。本研究调查了这些选定品系在基础焦虑行为或对酒精的抗焦虑反应方面是否与对照(HS)小鼠不同。我们还利用现有的近交系数据评估了黑暗中饮酒(DID)与基础焦虑样行为之间的遗传相关性。在进行DID测试后,立即在高架零迷宫上对雌雄两性的HDID重复品系(HDID - 1和HDID - 2)小鼠进行测试。总体而言,HDID小鼠在饮酒后在开放臂上花费的时间比HS小鼠更多,且开放臂时间与血液酒精浓度显著相关。HDID - 1雄性小鼠在基线(饮水对照)时也表现出较少的焦虑样行为。在另一个实验中,对HDID - 1和HS小鼠进行急性酒精注射的抗焦虑剂量反应测试。两种基因型都显示随着酒精剂量增加,在开放臂上花费的时间增加,并且在所有剂量下HDID - 1和雌性小鼠有更长的开放臂时间。HDID - 1对照雄性小鼠比HS对照雄性小鼠表现出更低的焦虑样行为。近交系数据分析还显示酒精DID与焦虑之间没有显著的遗传关系。这些发现表明,尽管第一批重复实验中的雄性小鼠有基础焦虑样行为减少的趋势,但HDID选择并未在焦虑样行为或对酒精诱导的抗焦虑作用的敏感性方面产生系统性变化。因此,焦虑状态和对酒精抗焦虑作用的敏感性似乎对HDID小鼠的高饮酒行为没有显著贡献。

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