Hulin Mary W, Amato Russell J, Porter Johnny R, Filipeanu Catalin M, Winsauer Peter J
Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112-1393, USA.
Adv Pharmacol Sci. 2011;2011:926361. doi: 10.1155/2011/926361. Epub 2011 Oct 31.
Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABA(A) receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will also present data collected by our laboratory showing that one neurosteroid in particular, dehydroepiandrosterone (DHEA), decreases ethanol intake in rats under a variety of conditions. In the process, we will also mention relevant studies from the literature suggesting that both particular subtypes and subunits of the GABA(A) receptor play an important role in mediating the interaction of neurosteroids and ethanol.
尽管在美国和欧洲酒精滥用及酒精依赖现象普遍存在，但获批用于治疗酒精依赖的药物疗法仅有五种。此外，这些药物治疗方案的临床效用有限。本文的目的是展示相关文献，表明酒精和神经甾体均作用于GABA(A)受体复合物，且该受体复合物上的神经甾体位点可作为开发新型酒精滥用治疗药物的新靶点。本文还将展示我们实验室收集的数据，表明一种特定的神经甾体，脱氢表雄酮（DHEA），在多种条件下均可减少大鼠的乙醇摄入量。在此过程中，我们还将提及文献中的相关研究，表明GABA(A)受体的特定亚型和亚基在介导神经甾体与乙醇的相互作用中均发挥重要作用。
