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首页> 外文期刊>Alcohol >Effects of ethanol and varenicline on female Sprague-Dawley rats in a third trimester model of fetal alcohol syndrome
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Effects of ethanol and varenicline on female Sprague-Dawley rats in a third trimester model of fetal alcohol syndrome

机译：乙醇和脉动线对胎儿酗酒综合征第三个三个月模型女性Sprague-Dawley大鼠的影响

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Perinatal ethanol?exposure disrupts a variety of developmental processes in neurons important for establishing a healthy brain. These ethanol-induced impairments known as fetal alcohol spectrum disorder (FASD) are not fully understood, and currently, there is no effective treatment. Further, growing evidence suggests that adult females are more susceptible to ethanol, with the effects of perinatal ethanol exposure also being sexually divergent. Female models have been historically underutilized in neurophysiological investigations, but here, we used a third-trimester binge-ethanol model of FASD to examine changes to basal forebrain (BF) physiology and behavior in female Sprague-Dawley rats. We also tested varenicline as a potential cholinomimetic therapeutic. Rat pups were gavage-treated with binge-like ethanol, varenicline and ethanol, and varenicline alone. Using patch-clamp electrophysiology in BF slices, we observed that binge-ethanol exposure increased spontaneous post-synaptic current (sPSC) frequency. Varenicline exposure alone also enhanced sPSC frequency. Varenicline plus ethanol co-treatment prevented the sPSC frequency increase. Changes in BF synaptic transmission persisted into adolescence after binge-ethanol treatment. Behaviorally, binge-ethanol treated females displayed increased anxiety (thigmotaxis) and demonstrated learning deficits in the water maze. Varenicline/ethanol co-treatment was effective at reducing these behavioral deficits. In the open field, ethanol-treated rats displayed longer distances traveled and spent less time in the center of the open field box. Co-treated rats displayed less anxiety, demonstrating a possible effect of varenicline on this measure. In conclusion, ethanol-induced changes in both BF synaptic transmission and behavior were reduced by varenicline in female rats, supporting a role for cholinergic therapeutics in FASD treatment.
机译：围产乙醇？暴露破坏神经元的各种发育过程，对于建立健康的大脑。这些称为胎儿酒精谱系障碍（FASD）的乙醇诱导的损伤尚未完全理解，目前没有有效的治疗方法。此外，日益增长的证据表明，成年女性更容易受到乙醇的影响，随着围产期乙醇暴露的影响也是性差异的影响。在历史上，在历史上未充分利用神经生理调查，但在这里，我们使用了第三孕孕孕酮的乙酰乙醇模型，以检查女性Sprague-Dawley大鼠的基础前脑（BF）生理学和行为的变化。我们还测试了varenicline作为潜在的胆碱治疗。用静像乙醇，varenIClin碱和乙醇，单独使用vAliClin碱和乙醇，以及单独的血管线。在BF切片中使用贴片电生理学，我们观察到泪乙醇暴露增加自发的突触后电流（SPSC）频率。单独的varenicline暴露也增强了SPSC频率。 varenicline加乙醇合作防止了SPSC频率增加。 BICE-乙醇处理后BF突触传递持续到青春期的变化。行为地，狂欢 - 乙醇治疗的女性显示出焦虑增加（ThigMotaxis），并在水迷宫中展示了学习缺陷。 varenicline /乙醇共治疗可有效降低这些行为缺陷。在开放领域，乙醇处理的大鼠在开放场箱中心延长行进并花费较少的时间。共同治疗的大鼠令人焦虑较少，展示了varenicline对这一措施的可能影响。总之，雌性大鼠中血管线减少了乙醇诱导的BF突触传播和行为的变化，支持对FasD治疗中的胆碱能治疗方法的作用。

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