Neurokinin 1 receptor antagonism as a possible therapy for alcoholism

George, David T.National Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)

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. 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 well-being, 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 in alcoholism.

Gilman, JodiNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)
Hersh, JacquelineNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)
Thorsell, AnnikaNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA(Swepub:liu)annth96 (author)
Herion, DavidNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)
Geyer, ChristopherNational Institutes of Health, Bethesda, NIH; Bethesda, MD, USA (author)
Peng, XiaomeiLilly Research Laboratories, Indianapolis, IN, USA (author)
Kielbasa, WilliamLilly Research Laboratories, Indianapolis, IN, USA (author)
Rawlings, RobertNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)
Brandt, John E.Lilly Research Laboratories, Indianapolis, IN, USA (author)
Gehlert, Donald R.Lilly Research Laboratories, Indianapolis, IN, USA (author)
Tauscher, Johannes T.Lilly Research Laboratories, Indianapolis, IN, USA (author)
Hunt, Stephen P.University College London, UK (author)
Hommer, DanielNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA (author)
Heilig, MarkusNational Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA(Swepub:liu)marhe41 (author)
National Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USANational Institutes of Health, Bethesda, NIH; Bethesda, MD, USA (creator_code:org_t)

In:Science: American Association for the Advancement of Science319:5869, s. 1536-15390036-80751095-9203

By the author/editor: George, David T.; Gilman, Jodi; Hersh, Jacquelin ...; Thorsell, Annika; Herion, David; Geyer, Christoph ...; show more...; Peng, Xiaomei; Kielbasa, Willia ...; Rawlings, Robert; Brandt, John E.; Gehlert, Donald ...; Tauscher, Johann ...; Hunt, Stephen P.; Hommer, Daniel; Heilig, Markus; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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