Ethanol-induced loss-of-righting response during ethanol withdrawal in male and female rats: associations with alterations in Arc labeling.

Ethanol-induced loss-of-righting response during ethanol withdrawal in male and female rats: associations with alterations in Arc labeling.
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雄性和雌性大鼠乙醇戒断期间乙醇诱导的失正反应:与 Arc 标记变化的关联。

DOI:
10.1111/j.1530-0277.2011.01613.x
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发表时间:
2012
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Devaud,LeslieL
Devaud,LeslieL
中科院分区:
--
文献类型:
--
作者:
Walls,ShawnA;Macklin,ZacharyL;Devaud,LeslieL

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背景:越来越多的证据表明,对乙醇的反应存在相关的性别差异。几项研究发现,在人类和各种动物模型中,乙醇戒断(EW)的表达和恢复存在差异。我们发现雌性大鼠比雄性大鼠恢复得更快,并且在戒断期间对各种行为评估和药理学挑战表现出不同的反应。本研究的目的是确定是否EW行为的性别差异扩展到急性乙醇administration.Methods的催眠作用:我们使用了一个重复测量设计,以评估时间和潜伏期为失去的翻正反射后,急性注射乙醇(4.2 g/kg; 20% w/v)对喂养的控制或乙醇撤出动物在1和3天EW的男性,女性和卵巢切除的女性(OVX)大鼠。  我们确定了蛋白质水平的活动调节的细胞骨架蛋白(弧),作为一个标记物的突触活动的突触能突触,在运动皮层和前额叶皮层在这些相同的治疗conditions.Results:乙醇撤出的动物有减少乙醇诱导的睡眠时间相比,对照组在1天EW。 睡眠时间仍然缩短,在3天EW的男性和OVX,但不是女性。 在所有性别条件下,运动皮质和视前核中的Arc蛋白水平在EW 1天时显著增加,表明与EW期间乙醇诱导的睡眠时间减少相关。弧水平进一步增加男性和OVX,但不是女性,在3天EW的时间点。结论:这些研究结果进一步支持性别差异的影响和响应乙醇。 他们认为,女性比男性更快地从EW中恢复也包括对乙醇催眠作用的耐受性表达。这些性别差异可能涉及一些差异性的神经适应性的amatergic信号。
Background:There is increasing evidence for relevant sex differences in responses to ethanol. Several investigations have found differences in expression and recovery from ethanol withdrawal (EW) in people and across various animal models. We have found that female rats recover more quickly than male rats and show differential responses to various behavioral assessments and pharmacological challenges during withdrawal. The purpose of this study was to determine whether sex differences in EW behaviors extend to the hypnotic effects of acute ethanol administration.Methods:We used a repeated measures design to assess duration and latency for loss‐of‐righting reflex following an acute injection of ethanol (4.2 g/kg; 20% w/v) to pair‐fed control or ethanol‐withdrawn animals at 1 and 3 days EW in male, female, and ovariectomized female (OVX) rats. We determined protein levels of the activity‐regulated cytoskeletal protein (Arc), used as a marker for synaptic activity in glutamatergic synapses, in the motor cortex and prefrontal cortex across these same treatment conditions.Results:Ethanol‐withdrawn animals had a reduced ethanol‐induced sleep time compared to controls at 1 day EW. Sleep time remained shortened at 3 days EW for males and OVX, but not females. Arc protein levels in motor cortex and preoptic nuclei significantly increased at 1 day EW across all sex conditions, suggestive of an association with the reduced ethanol‐induced sleep times during EW. Arc levels increased further for males and OVX, but not females, at the 3 days EW time point.Conclusions:These findings add further support to sex differences in effects of and responses to ethanol. They suggest that the more rapid recovery from EW for females than males also includes expression of tolerance to the hypnotic effects of ethanol. These sex differences may involve some differential neuroadaptations in glutamatergic signaling.