Sex differences in rats in the development of and recovery from ethanol dependence assessed by changes in seizure susceptibility
Sex differences in rats in the development of and recovery from ethanol dependence assessed by changes in seizure susceptibility
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DOI：
10.1097/00000374-200111000-00017
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发表时间：
2001-11-01
影响因子：
3.2
通讯作者：
Chadda, R
中科院分区：
文献类型：
--
作者：
Devaud, LL;Chadda, R
背景：先前的研究发现大鼠对长期乙醇暴露的反应存在性别差异。在乙醇戒断期间，抗惊厥治疗观察到最显着的差异，此时癫痫发作的易感性显着增加。 GABA 能和谷氨酸能化合物的这种反应存在性别差异。本研究旨在探讨性别是否也会影响乙醇依赖的发展和恢复时间。方法：以流质饮食给予乙醇，配对喂养的动物接受葡萄糖等热量替代乙醇。通过测量突然去除乙醇饮食后的癫痫阈值来评估乙醇依赖和戒断。通过尾静脉缓慢输注γ-氨基丁酸(A)-受体拮抗剂荷包牡丹碱来确定癫痫阈值。结果：雄性和雌性大鼠在乙醇依赖的发作和恢复时间上表现出差异，这通过乙醇戒断癫痫易感性的变化来确定。与雄性大鼠相比，雌性大鼠产生依赖性较慢，恢复较快。此外，急性乙醇给药不会改变配对喂养对照动物的癫痫易感性，但对乙醇戒断大鼠具有抗惊厥作用。与雄性大鼠相比，戒断乙醇的雌性大鼠对急性乙醇给药表现出更大的反应。结论：这组实验揭示了乙醇依赖和戒断的一项指标中存在额外的性别差异。所提出的乙醇依赖性发展机制涉及γ-氨基丁酸(A) 和NMDA 受体亚基组装的改变或各种翻译后修饰。考虑到这些发现，无论乙醇依赖的发展机制如何，雄性大鼠与雌性大鼠相比都有不同的事件顺序。正在进行研究以确定乙醇依赖/戒断的行为测量与选择性神经元适应之间的关联。
Background: Previous investigations have found sex differences in rats in response to chronic ethanol exposure. The most dramatic differences were observed with anticonvulsant treatment during ethanol withdrawal, when seizure susceptibility is significantly increased. Sex differences in this response were found for both GABAergic and glutamatergic compounds. This study was aimed at exploring whether sex also influences the timing for the development of and recovery from ethanol dependence.Methods: Ethanol was administered in a liquid diet, with pair-fed animals receiving dextrose, substituted isocalorically for the ethanol. Ethanol dependence and withdrawal were assessed by measurement of seizure thresholds after abrupt removal of the ethanol diet. Seizure thresholds were determined by slow, tail vein infusion of the gamma -aminobutyric acid(A)-receptor antagonist bicuculline.Results: Male and female rats displayed differences in timing for both onset and recovery from ethanol dependence, as determined by changes in ethanol withdrawal seizure susceptibility. Female rats were slower to develop dependence and quicker to recover compared with male rats. Furthermore, acute ethanol administration did not alter seizure susceptibility in pair-fed control animals, but it was anticonvulsant in ethanol-withdrawn rats. Ethanol-withdrawn female rats showed a greater response to acute ethanol administration than did male rats.Conclusions: This set of experiments uncovered additional sex differences in one measure of ethanol dependence and withdrawal. Proposed mechanisms for the development of ethanol dependence involve alterations in subunit assembly of gamma -aminobutyric acid(A) and NMDA receptors or various posttranslational modifications. In consideration of these findings, whatever mechanisms underlie the development of ethanol dependence, there is a different sequence of events in male compared with female rats. Studies are ongoing to determine associations between behavioral measures of ethanol dependence/withdrawal and selective neuronal adaptations.