Sex differences in steroid modulation of ethanol withdrawal in male and female rats
Sex differences in steroid modulation of ethanol withdrawal in male and female rats
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DOI：
10.1124/jpet.106.107896
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Devaud, L. L.
中科院分区：
文献类型：
--
作者：
Alele, P. E.;Devaud, L. L.
我们研究了神经活性类固醇，双烯醇酮，和卵巢类固醇，17 β-雌二醇，在乙醇戒断（EW）的两个时间点癫痫发作的表达。这两种类固醇都可以对大脑产生快速的非基因组作用，包括癫痫发作活动的调节。因为它们的基础水平在成年男性和女性中不同，EW的主要症状是癫痫发作风险增加，我们想确定这些类固醇在EW期间是否具有抗惊厥作用。通过在营养完全的流质饮食中给予6%乙醇14天，使大鼠产生乙醇依赖性。在去除含乙醇的饮食后，在第1或3天测试EW和配对对照大鼠对戊四唑的癫痫发作反应。与以前的报告一致，女性似乎比男性更快地从EW中恢复过来。我们观察到显着的性别差异的反应类固醇，主要是在3天EW。孕烯醇酮提供了更大的影响，在EW期间比在控制条件下，更大的影响，在女性比男性大鼠癫痫发作的保护。相比之下，雌二醇的效果好坏参半。卵巢切除雌性大鼠的一些反应与完整雌性大鼠相似，而其他反应与雄性大鼠更相似。我们的行为研究结果与观察到的EW诱导的血浆皮质酮水平变化一致，显示雄性大鼠而非雌性大鼠持续升高。这些结果支持和扩展早期的研究结果表明，虽然激素环境的影响EW，先天差异的大脑结构之间的性别也有助于EW的性别差异。
We investigated the actions of the neuroactive steroid, pregnenolone, and the ovarian steroid, 17 beta- estradiol, on seizure expression during two time points of ethanol withdrawal ( EW). Both steroids can exert rapid, nongenomic actions on the brain that include modulation of seizure activity. Because their basal levels differ in adult males and females and a major symptom of EW is increased seizure risk, we wanted to determine whether these steroids were anticonvulsant during EW. Rats were made ethanol-dependent by administration of 6% ethanol in a nutritionally complete liquid diet for 14 days. After removal of the ethanol- containing diet, EW and paired control rats were tested at 1 or 3 days for seizure responses to pentylenetetrazol. Consistent with previous reports, females seemed to have recovered from EW more quickly than males. We observed significant sex differences in responses to the steroids, primarily at 3 days EW. Pregnanolone afforded protection against seizures with larger effects during EW than in control conditions and greater effects in female than male rats. In contrast, effects of estradiol were mixed. Some responses of ovariectomized female rats were similar to intact females, whereas other responses were more similar to males. Our behavioral findings are consistent with observed EW- induced changes in plasma corticosterone levels, showing persistent elevations in male but not female rats. These results support and extend earlier findings suggesting that although the hormonal milieu influences EW, innate differences in brain structure between the sexes also contribute to sex differences in EW.