Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, USA.
Alcohol Clin Exp Res. 2012 Feb;36(2):234-41. doi: 10.1111/j.1530-0277.2011.01613.x. Epub 2011 Sep 6.
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.
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for loss-of-righting reflex following an acute injection of ethanol (4.2 g/kg; 20% w/v) to pair-fed control or ethanol-withdrawn animals at 1 and 3 days EW in male, female, and ovariectomized female (OVX) rats.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.
Ethanol-withdrawn animals had a reduced ethanol-induced sleep time compared to controls at 1 day EW.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.
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.
越来越多的证据表明，乙醇的反应存在相关的性别差异。一些研究发现，人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物挑战有不同的反应。本研究的目的是确定 EW 行为中的性别差异是否扩展到急性乙醇给药的催眠作用。
我们使用重复测量设计来评估在 1 天和 3 天 EW 时，给予急性乙醇（4.2g/kg；20%w/v）后，配对喂养的对照或乙醇戒断动物的右反转反射丧失持续时间和潜伏期，雄性、雌性和卵巢切除雌性（OVX）大鼠。我们在相同的治疗条件下，确定运动皮层和前额叶皮层中活性调节细胞骨架蛋白（Arc）的蛋白水平，Arc 作为谷氨酸能突触中突触活动的标志物。
与对照组相比，1 天 EW 时，乙醇戒断动物的乙醇诱导睡眠时间缩短。雄性和 OVX 的睡眠时间在 3 天 EW 时仍缩短，但雌性则不然。所有性别条件下，1 天 EW 时，运动皮层和视前核中的 Arc 蛋白水平显著升高，提示与 EW 期间乙醇诱导睡眠时间缩短有关。Arc 水平在雄性和 OVX 进一步升高，但在雌性中没有升高。
这些发现进一步支持了乙醇作用和反应中的性别差异。它们表明，女性比男性从 EW 中更快恢复，这也包括对乙醇催眠作用的耐受性。这些性别差异可能涉及谷氨酸能信号传递的一些不同的神经适应。
