Division of Neuroscience, Oregon National Primate Research Center Beaverton, OR, USA.
Front Endocrinol (Lausanne). 2012 Jan 31;3:10. doi: 10.3389/fendo.2012.00010. eCollection 2012.
This review will highlight a variety of mechanisms by which neurosteroids affect sensitivity to ethanol, including physiological states associated with activity of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes, and the effects of chronic exposure to ethanol, in addition to behavioral implications. To date, γ-aminobutyric acid (GABA(A)) receptor mechanisms are a major focus of the modulation of ethanol effects by neuroactive steroids. While NMDA receptor mechanisms are gaining prominence in the literature, these complex data would be best discussed separately. Accordingly, GABA(A) receptor mechanisms are emphasized in this review with brief mention of some NMDA receptor mechanisms to point out contrasting neuroactive steroid pharmacology. Overall, the data suggest that neurosteroids are virtually ubiquitous modulators of inhibitory neurotransmission. Neurosteroids appear to affect sensitivity to ethanol in specific brain regions and, consequently, specific behavioral tests, possibly related to the efficacy and potency of ethanol to potentiate the release of GABA and increase neurosteroid concentrations. Although direct interaction of ethanol and neuroactive steroids at common receptor binding sites has been suggested in some studies, this proposition is still controversial. It is currently difficult to assign a specific mechanism by which neuroactive steroids could modulate the effects of ethanol in particular behavioral tasks.
这篇综述将重点介绍神经甾体影响乙醇敏感性的多种机制，包括与下丘脑-垂体-肾上腺（HPA）和下丘脑-垂体-性腺（HPG）轴活性相关的生理状态，以及慢性乙醇暴露的影响，此外还将讨论其行为学意义。迄今为止，γ-氨基丁酸（GABA(A))受体机制是神经活性甾体调节乙醇作用的主要焦点。虽然 NMDA 受体机制在文献中越来越受到关注，但这些复杂的数据最好单独讨论。因此，本综述重点介绍 GABA(A)受体机制，并简要提及一些 NMDA 受体机制，以指出相反的神经活性甾体药理学。总的来说，这些数据表明神经甾体实际上是抑制性神经传递的普遍调节剂。神经甾体似乎会影响特定脑区对乙醇的敏感性，从而影响特定的行为测试，这可能与乙醇增强 GABA 释放和增加神经甾体浓度的功效和效力有关。尽管在一些研究中已经提出了乙醇和神经活性甾体在共同受体结合位点的直接相互作用，但这一观点仍存在争议。目前，很难确定神经活性甾体在特定行为任务中调节乙醇作用的具体机制。
