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Brain Stress System Presents Possible Treatment Target for Alcohol Dependence
A brain circuit that underlies feelings of stress and anxiety shows promise as a new therapeutic target for alcoholism, according to new studies by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).
In preclinical and clinical studies currently reported online in Science Express, NIAAA Clinical Director Markus Heilig, M.D., Ph.D., and colleagues from the NIH, Lilly Research Laboratories, and University College in London found that a brain molecule known as the neurokinin 1 receptor, or NK1R, appears to be a central actor in stress-related drinking.
The researchers first demonstrated that NK1R plays an integral role in alcohol consumption in animals. Mice that were genetically engineered to lack NK1 receptors consumed much less alcohol than did normal mice with fully functional NK1R. Subsequently, in a small clinical study, the
researchers showed that an experimental compound designed to block NK1 receptors reduced alcohol craving and improved overall well being among recently detoxified alcohol-dependent individuals who had high levels of anxiety. Using functional brain imaging, the researchers also showed that the exaggerated sensitivity to negative stimuli seen in alcoholics was dampened with the medication, while the lack of responses to pleasurable stimuli was restored.
"This work exemplifies the NIH's unique capacity for speeding the translation of promising laboratory discoveries into potential new medical treatments," notes NIH Director Elias Zerhouni, M.D.
"These findings advance our understanding of the link between stress and alcohol dependence and raise the prospect of a new class of medications for treating alcoholism," adds NIAAA Director Ting-Kai Li, M.D.
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