Homer2 regulates alcohol and stress cross-sensitization.
Homer2 regulates alcohol and stress cross-sensitization.
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DOI：
10.1111/adb.12252
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Quadir SG;Santos JR;Campbell RR;Wroten MG;Singh N;Holloway JJ;Bal SK;Camarini R;Szumlinski KK
在酒精使用障碍的病因和慢性病程中，压力和酒精之间存在相互作用；然而，对于这种相互作用的神经生物学基础，我们还存在知识空白。在这方面，我们采用了为期11天的不可预测的慢性轻度应激（UCMS）程序，以研究运动活动的压力 - 酒精交叉敏感化，以及酒精摄入/偏好和醉酒情况。我们还采用免疫印迹法，将伏隔核（NAC）各亚区的谷氨酸受体相关蛋白的表达与行为交叉敏感化的表现联系起来。与未受应激的对照组相比，UCMS小鼠对急性注射2 g/kg酒精表现出更强的运动反应，这种交叉敏感化还延伸到酒精摄入量（0 - 20%），以及分别对3 g/kg和5 g/kg酒精的中毒和镇静特性。无论之前是否注射酒精（2 g/kg），UCMS小鼠在NAC壳部的mGlu1α、GluN2b和Homer2水平均升高，而该亚区内的PLCβ水平较低。UCMS小鼠的NAC核心区内的GluN2b水平也较低。压力 - 酒精运动交叉敏感化的表现与NAC核心区的mGlu1α水平较低以及两个NAC亚区内的ERK活性较低有关。由于Homer2调节酒精敏感化，我们还在Homer2野生型（WT）和敲除型（KO）小鼠中检测了运动交叉敏感化。WT小鼠表现出非常强烈的交叉敏感化，而KO动物则没有。这些结果表明，轻度应激史使动物对酒精的精神运动和奖赏特性更加敏感，这可能取决于NAC谷氨酸传递中的神经可塑性。
An interaction exists between stress and alcohol in the etiology and chronicity of alcohol use disorders; yet a knowledge gap exists regarding the neurobiological underpinnings of this interaction. In this regard, we employed an 11-day unpredictable, chronic, mild stress (UCMS) procedure to examine for stress-alcohol cross-sensitization of motor activity, as well as alcohol consumption/preference and intoxication. We also employed immunoblotting to relate the expression of glutamate receptor-related proteins within subregions of the nucleus accumbens (NAC) to the manifestation of behavioral cross-sensitization. UCMS mice exhibited a greater locomotor response to an acute injection of 2 g/kg alcohol than unstressed controls and this cross-sensitization extended to alcohol intake (0–20%), as well as to the intoxicating and sedative properties of 3 and 5 g/kg alcohol, respectively. Regardless of prior alcohol injection (2 g/kg), UCMS mice exhibited elevated NAC shell levels of mGlu1α, GluN2b and Homer2, as well as lower PLCβ within this subregion. GluN2b levels were also lower within the NAC core of UCMS mice. The expression of stress-alcohol locomotor cross-sensitization was associated with lower mGlu1α within the NAC core and lower ERK activity within both NAC subregions. As Homer2 regulates alcohol sensitization, we assayed also for locomotor cross-sensitization in Homer2 wild-type (WT) and knock-out (KO) mice. WT mice exhibited a very robust cross-sensitization, that was absent in KO animals. These results indicate that a history of mild stress renders an animal more sensitive to the psychomotor and rewarding properties of alcohol, which may depend upon neuroplasticity within NAC glutamate transmission.
影响因子：
4.7
作者：
Lee MR;Bollinger JW;Leggio L
通讯作者：
Leggio L