根據(jù)一項在小鼠及病人身上開展的新的研究顯示(這些小鼠和人最近經(jīng)歷了戒除酒精成癮的治療)，一種對大腦產(chǎn)生的部分行為應激反應有抑制作用的藥物可能成為一種治療酗酒的有效方法,。盡管諸如Alcoholics Anonymous等心理社會干預取得了成功,，但長期酗酒仍然是一個明顯的公共衛(wèi)生方面的問題，因而,，研究人員對研發(fā)互補性的藥物療法很有興趣,。注意到應激是酗酒復發(fā)的一個激發(fā)因素，David George及其同事針對是否能夠對神經(jīng)激肽I受體(NK1R)進行藥理抑制來減輕與酒精依賴有關的癥狀進行了探索(NK1R是腦應激反應的一種介質),。在證明了NKIR遺傳缺陷的小鼠比對照組小鼠攝入的酒精要少之后,，研究人員在一個小型的設有對照組的研究中，對最近接受戒酒治療的住院病人給予了某種能夠拮抗NK1R的藥物,，并對其效應進行了調查,。(科學時報)
生物谷推薦英文原文：
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: [email protected]
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.
