Alcohol is the most common addictive substance worldwide, and its excessive use leads to chronic diseases, social issues, and an estimated 88,000 deaths each year in the U.S., costing $249 billion. More than 14 million people in the U.S. suffer from alcohol use disorder, but the disorder is under-treated, with only three effective pharmacological therapies available.
The brain’s Neuroadaptive response to long-term alcohol exposure leads to changes in key stress neurotransmitters, particularly in the “bed nucleus of the stria terminalis” (BNST) area of the brain. Researchers at Boston University Chobanian & Avedisian School of Medicine have identified that the peptide pituitary adenylate cyclase activating polypeptide (PACAP) is involved in heavy alcohol drinking and acts in the BNST area.
The researchers observed increased levels of the stress neuropeptide PACAP and the related stress neuropeptide CGRP in the BNST during withdrawal in a model for heavy, intermittent alcohol drinking, as compared to the control model. Using a virus in a transgenic model to block the neural pathways containing PACAP specifically arriving in the BNST, they found that inhibiting PACAP reduced heavy ethanol drinking.
These results indicate that PACAP plays a role in driving heavy alcohol drinking and can be targeted for the development of novel pharmacological therapies. The findings of this study have been published in the journal eNeuro.
The study was funded by grants from the National Institute on Alcohol and Alcoholism (NIAAA), the Boston University Undergraduate Research Opportunities Program (UROP), the Boston University Micro, and Nano Imaging Facility, and the National Institutes of Health (S10OD024993). The research was conducted at Boston University School of Medicine.
In conclusion, this study uncovers the involvement of PACAP in heavy alcohol drinking and provides insights that could lead to the development of new pharmacological treatments for alcohol addiction.