Ethanol-related behaviors in mice lacking the sigma-1 receptor.
Ethanol-related behaviors in mice lacking the sigma-1 receptor.
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DOI：
10.1016/j.bbr.2015.10.013
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发表时间：
2016-01-15
影响因子：
2.7
通讯作者：
Sabino V
中科院分区：
文献类型：
--
作者：
Valenza M;DiLeo A;Steardo L;Cottone P;Sabino V
Sigma-1受体(Sigma-1R)是一种伴侣蛋白，与药物滥用和成瘾有关。多项研究已经确定了SIG-1R在精神刺激剂成瘾中的作用，但专门研究其在酒精成瘾中的作用的研究较少。我们之前已经证明，SIG-1R的拮抗作用可以减少过度饮酒和饮酒动机，而激动型则会诱导啮齿类动物暴饮暴食。这些研究的目的是探讨C57BL/6J小鼠Sig-1R基因缺失对饮酒和其他酒精相关行为的影响。我们使用了一组广泛的行为测试来检验缺乏Oprs1的成年雄性小鼠的酒精行为。Oprs1是编码SIG-1R的基因。为了比较SIG-1基因敲除(KO)和野生型(WT)小鼠的饮酒行为，对SIG-1基因敲除(KO)和野生型(WT)小鼠进行了两瓶选择、不同浓度乙醇(3%-20%v/v)和水的连续饮酒范式。在Sig-1R、KO和WT小鼠中也评估了甜味和苦味溶液的摄入量。最后对乙醇的运动刺激性、味觉厌恶和共济失调效应进行了评估。与WT小鼠相比，SIG-1R KO小鼠表现出更高的酒精摄入量；这两种基因型的小鼠在甜味或苦味感受上没有差异。SIG-1R KO小鼠对乙醇刺激效应的敏感性较低，但对其味觉厌恶效应的敏感性较高。在突变体中，乙醇诱导的镇静作用没有改变。我们的结果表明，Sig-1R的缺失增加了乙醇的消耗，可能是通过减少其奖励效应，从而表明Sig-1R参与了酒精增强效应的调节。
The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulants addiction, but fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3%–20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was unaltered in the mutants. Our results suggest that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol.