Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism

• DOI: 10.1126/science.1153813
• Publication Date: 2008-02-15T02:29:39Z
• Authors: David T. George; Jodi Gilman; Jacqueline Hersh; Annika Thorsell; David Herion; Christopher Geyer; Xiaomei Peng; William Kielbasa; Robert Rawlings; John E. Brandt; Donald R. Gehlert; Johannes T. Tauscher; Stephen P. Hunt; Daniel Hommer; Markus Heilig
• Keywords: Adult; Male; 0303 health sciences; Alcohol Drinking; Ethanol; Hydrocortisone; Pyridines; Emotions; Brain; Middle Aged; Receptors, Neurokinin-1; Magnetic Resonance Imaging; 3. Good health; Behavior, Addictive; Mice, Inbred C57BL; Alcoholism; Mice; 03 medical and health sciences; Neurokinin-1 Receptor Antagonists; Animals; Humans; Female; Aged

Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems the brain play an increasing role motivating continued alcohol use and relapse. We investigated neurokinin 1 receptor (NK1R), mediator behavioral responses, treatment. In preclinical studies, mice genetically deficient NK1R showed marked decrease voluntary consumption had increased sensitivity to sedative effects alcohol. randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with antagonist (LY686017; n = 25) or placebo ( 25). LY686017 suppressed spontaneous cravings, improved overall well-being, blunted cravings induced by procedure, attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses affective stimuli likewise suggested beneficial effects. Thus, as assessed these surrogate markers efficacy, antagonism warrants further investigation treatment alcoholism.