PNAS：催产素或可让醉酒者清醒过来

  催产素，有时候被称之为性激素或“拥抱激素”，由于其在社会行为和性行为中扮演着重要的角色，因此其在流行文化中占据着传奇的地位；近日，一项刊登在PNAS上的研究论文中，来自悉尼大学等处的研究人员通过研究发现催产素会明显影响酒精对机体的麻醉效应。
  文章中当研究人员将催产素灌输到给予酒精的大鼠大脑中后他们发现，催产素可以抑制酒精引发的机体协调性的缺失，研究者Bowen说道，在清醒测试中同时给予催产素和酒精的大鼠则会顺利完成测试，而仅给予酒精的大树则会出现严重的测试问题。催产素可抑制酒精进入到大脑的特殊位点，从而抑制酒精的麻醉效应，而大脑中的该位点名为δ-亚单位GABA-A受体。
  酒精会通过抑制大脑中提供运动控制的区域的活性来损伤机体的协调性，而催产素则可抑制酒精的这种效应，其使得机体“清醒过来”的这种效应在人类机体中也到了证实，但是研究者希望通过更为深入的研究来揭示其中的分子机理。首先研究者希望开发一种药物运输的方法来将足量的催产素运输到达人类大脑，如果成功的话那么研究者猜测，催产素会在个体摄入大量酒精后尽可能减少酒精对大脑言语和认知能力的损伤。
  值得注意的，在你从酒吧喝完酒开车回家的过程中催产素并不能帮助你躲避警察的检查，当催产素降低机体沉醉水平时，实际上其并不能改变血液中的酒精水平，这是因为催产素是通过抑制血液进入机体大脑来发挥作用的，其并不会加速酒精从机体中排泄掉。因此有些人就担心降低机体酒醉状态的药物是否就意味着鼓励个体多饮酒？实际上研究者进行研究发现摄入催产素实际上仅能帮助减少酒精的消耗和渴求度。
  最后研究者Bowen说道，我们认为催产素对酒精消耗和渴求度的效应是通过在大脑中的一种类似的机制来实现的，而该研究也为后期开发基于催产素的新型疗法来治疗酒精使用障碍的患者提供思路和希望。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Oxytocin prevents ethanol actions at {delta} subunit-containing GABAA receptors and attenuates ethanol-induced motor impairment in rats
PNAS    doi: 10.1073/pnas.1416900112
Michael T. Bowena,b,1, Sebastian T. Petersc,1, Nathan Absalomb, Mary Chebibb, Inga D. Neumannc, and Iain S. McGregora,2
Even moderate doses of alcohol cause considerable impairment of motor coordination, an effect that substantially involves potentiation of GABAergic activity at δ subunit-containing GABAA receptors (δ-GABAARs). Here, we demonstrate that oxytocin selectively attenuates ethanol-induced motor impairment and ethanol-induced increases in GABAergic activity at δ-GABAARs and that this effect does not involve the oxytocin receptor. Specifically, oxytocin (1 µg i.c.v.) given before ethanol (1.5 g/kg i.p.) attenuated the sedation and ataxia induced by ethanol in the open-field locomotor test, wire-hanging test, and righting-reflex test in male rats. Using two-electrode voltage-clamp electrophysiology in Xenopus oocytes, oxytocin was found to completely block ethanol-enhanced activity at α4β1δ and α4β3δ recombinant GABAARs. Conversely, ethanol had no effect when applied to α4β1 or α4β3 cells, demonstrating the critical presence of the δ subunit in this effect. Oxytocin had no effect on the motor impairment or in vitro effects induced by the δ-selective GABAAR agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, which binds at a different site on δ-GABAARs than ethanol. Vasopressin, which is a nonapeptide with substantial structural similarity to oxytocin, did not alter ethanol effects at δ-GABAARs. This pattern of results confirms the specificity of the interaction between oxytocin and ethanol at δ-GABAARs. Finally, our in vitro constructs did not express any oxytocin receptors, meaning that the observed interactions occur directly at δ-GABAARs. The profound and direct interaction observed between oxytocin and ethanol at the behavioral and cellular level may have relevance for the development of novel therapeutics for alcohol intoxication and dependence.