• DOI:10.1126/science.1153813
• Corpus ID: 206510823

Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism

@article{George2008Neurokinin1R,
  title={Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism},
  author={David Ted George and Jodi M. Gilman and Jacqueline Hersh and Annika Thorsell and David Herion and Christopher Geyer and Xiaomei Peng and William Kielbasa and Robert R. Rawlings and John E Brandt and Donald R. Gehlert and Johannes T. Tauscher and Stephen P Hunt and Daniel W. Hommer and Markus Heilig},
  journal={Science},
  year={2008},
  volume={319},
  pages={1536 - 1539}
}

• D. George, J. Gilman, +12 authors M. Heilig
• Published 14 March 2008
• Medicine
• Science

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.