Differences between male and female rats in alcohol drinking, negative affects and neuronal activity after acute and prolonged abstinence.

International journal of physiology, pathophysiology and pharmacology Pub Date : 2019-08-25 eCollection Date: 2019-01-01
Jing Li, Pei Chen, Xiao Han, Wanhong Zuo, Qinghua Mei, Emily Yao Bian, Jennifer Umeugo, Jianghong Ye
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Abstract

Alcohol consumption afflicts men and women differently. However, the underlying neuronal mechanisms that contribute to the difference are mostly unexplored. Although more men suffer from alcohol use disorders (AUD), women more frequently accelerate to dependence and develop adverse consequences of alcoholism sooner than men. Women also exhibit more significant negative emotions that cues more reactivity and alcohol-craving than men. Despite ample evidence that women are vulnerable to AUD, results of preclinical studies on sex differences in alcohol consumption and withdrawal-related behaviors are inconclusive. In this study, we trained adult male and female Sprague-Dawley rats to drink alcohol in the intermittent access to 20% ethanol two-bottle free-choice paradigm for two months. Their behaviors and Fos expression in related brain regions were measured at acute (24 h) and after prolonged (28 days) abstinence. We found that female rats drank more alcohol than males. After acute abstinence, rats of both sexes showed higher sensitivity to depressive, thermal, and mechanical stimuli. Females also displayed higher anxiety levels. After prolonged abstinence, rats of both sexes displayed depressive-like behaviors; the males displayed allodynia; the females showed higher anxiety levels and drank more alcohol upon reaccess to alcohol. Furthermore, during acute withdrawal, Fos-positive nuclei were increased in the prefrontal cortex, anterior cingulate cortex (ACC), nucleus accumbens (NAc), amygdala and lateral habenula (LHb) in the females, versus only in the ACC, amygdala, and LHb in the males. Conversely, after prolonged abstinence, Fos-positive nuclei were decreased in the prefrontal cortex, ACC, and NAc in the females, but fell in the ACC, NAc, and LHb of the males. Thus, adaptations in diverse brain regions may contribute to the sex differences in behaviors in ethanol-withdrawn rats.

急性和长期戒酒后雌雄大鼠在饮酒、负面影响和神经元活动方面的差异。
饮酒对男性和女性的影响是不同的。然而,造成这种差异的潜在神经元机制大多尚未得到研究。尽管罹患酒精使用障碍(AUD)的男性更多,但女性比男性更容易加速对酒精的依赖,并更早出现酗酒的不良后果。与男性相比,女性也会表现出更多的负面情绪,从而引发更多的反应和对酒精的渴望。尽管有大量证据表明女性容易罹患 AUD,但有关酒精消费和戒断相关行为的性别差异的临床前研究结果尚无定论。在本研究中,我们对成年雄性和雌性 Sprague-Dawley 大鼠进行了为期两个月的间歇性获取 20% 乙醇双瓶自由选择范式的饮酒训练。在急性戒酒(24 小时)和长期戒酒(28 天)后,对它们的行为和相关脑区的 Fos 表达进行了测量。我们发现,雌性大鼠比雄性大鼠饮酒更多。急性戒酒后,雌雄大鼠对抑郁、热和机械刺激都表现出更高的敏感性。雌性还表现出更高的焦虑水平。长期戒酒后,雌雄大鼠都表现出类似抑郁的行为;雄性大鼠表现出异触症;雌性大鼠表现出更高的焦虑水平,并且在再次接触酒精时饮酒量更大。此外,在急性戒断期间,雌性大鼠的前额叶皮层、前扣带回皮层(ACC)、伏隔核(NAc)、杏仁核和侧脑室(LHb)中的Fos阳性核增加,而雄性大鼠仅在ACC、杏仁核和侧脑室中增加。相反,长期禁欲后,女性前额叶皮层、ACC和NAc中的Fos阳性核减少,而男性的ACC、NAc和LHb中的Fos阳性核减少。因此,不同脑区的适应可能是导致乙醇戒断大鼠行为性别差异的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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