根据一项在小鼠及病人身上开展的新的研究显示(这些小鼠和人最近经历了戒除酒精成瘾的治疗)，一种对大脑产生的部分行为应激反应有抑制作用的药物可能成为一种治疗酗酒的有效方法。尽管诸如Alcoholics Anonymous等心理社会干预取得了成功，但长期酗酒仍然是一个明显的公共卫生方面的问题，因而，研究人员对研发互补性的药物疗法很有兴趣。注意到应激是酗酒复发的一个激发因素，David George及其同事针对是否能够对神经激肽I受体(NK1R)进行药理抑制来减轻与酒精依赖有关的症状进行了探索(NK1R是脑应激反应的一种介质)。在证明了NKIR遗传缺陷的小鼠比对照组小鼠摄入的酒精要少之后，研究人员在一个小型的设有对照组的研究中，对最近接受戒酒治疗的住院病人给予了某种能够拮抗NK1R的药物，并对其效应进行了调查。(科学时报)
生物谷推荐英文原文：
Published Online February 14, 2008
Science DOI: 10.1126/science.1153813
Submitted on December 5, 2007
Accepted on February 8, 2008
Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism
David T. George 1, Jodi Gilman 1, Jacqueline Hersh 1, Annika Thorsell 1, David Herion 1, Christopher Geyer 2, Xiaomei Peng 3, William Kielbasa 3, Robert Rawlings 1, John E. Brandt 3, Donald R. Gehlert 3, Johannes T. Tauscher 3, Stephen P. Hunt 4, Daniel Hommer 1, Markus Heilig 1*
1 Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
2 Department of Nursing, Mark O. Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
3 Lilly Research Laboratories, Indianapolis, IN 46285, USA.
4 Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, UK.
* To whom correspondence should be addressed.
Markus Heilig , E-mail: markus.heilig@mail.nih.gov
These authors contributed equally to this work.
Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. Here, we investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall wellbeing, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment target in alcoholism.
