New research supported by the National Institutes of Health shows how elements of the brain’s stress and reward pathways can interact to suppress binge alcohol drinking. The finding, now online in the journal Nature Neuroscience, suggests potential strategies for treating and preventing alcohol use problems.
“This study is an important contribution to our knowledge of the neurobiology of alcohol use disorders and could open new avenues for medication development,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the primary sponsor of the research. NIH’s National Institute of Diabetes and Digestive and Kidney Diseases also provided support for the study.
Binge alcohol drinking contributes to myriad acute and chronic public health problems, and accounts for an estimated three-quarters of the total economic cost of alcohol misuse. Accumulating evidence indicates that binge drinking by adolescents and college students contributes to alcohol dependence and anxiety disorders.
Previous studies have shown that brain signaling by a protein known as corticotropin-releasing factor (CRF) increases anxiety. CRF activity also increases during binge alcohol drinking. In contrast, a brain protein called neuropeptide Y (NPY) is known to reduce binge drinking and anxiety. However, how and where these two opposing systems interact in the brain is unknown.
The current study reports that the anti-drinking effect of NPY is produced by enhancing the inhibition of CRF neurons in a brain region – the bed nucleus of the stria terminalis, or BNST — that is involved in reward and anxiety behaviors. Researchers led by Thomas L. Kash, Ph.D., at the University of North Carolina’s Bowles Center for Alcohol Studies, Chapel Hill, used multi-faceted approaches in animal models of binge and chronic drinking to define NPY’s role in the BNST.
“We found that NPY inhibited a specific population of cells in the BNST that produce CRF,” explained Dr. Kash. “When we then mimicked the actions of NPY using engineered proteins, we were also able to suppress binge alcohol drinking in mice. Finally, we found that this anti-drinking NPY system is altered by long-term alcohol drinking in multiple species, suggesting that this may be either a potential biomarker or treatment target for alcohol abuse or dependence.”
Results of this study provide direct evidence that NPY signaling is involved in binge alcohol drinking. It also indicates that previously reported divergent alcohol-drinking effects of NPY and CRF activation may be due to their opposing functional roles in the BNST. The findings suggest that enhancing NPY function or inhibiting CRF function could be useful strategies for preventing and treating alcohol use disorders.