Peptide is a key mediator in the regulation of compulsive alcohol drinking

November 16, 2020

(Boston)--Researchers from Boston University School of Medicine (BUSM) have identified that a peptide, pituitary adenylate cyclase-activating mediator of compulsive consumption of alcohol. In addition, they have discovered that this protein acts in an area of the brain called the Bed Nucleus of the Stria Terminalis, or BNST, a region involved in fear, anxiety and stress responses, to exert these effects.

Alcohol use disorder or AUD is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational or health consequences. An estimated 15 million people in the U.S. have AUD. Approximately 5.8 percent or 14.4 million adults in the U.S. ages 18 and older had AUD in 2018, including 9.2 million men and 5.3 million women.

Comparing two experimental models, the researchers observed anxiety-like behavior and spontaneous compulsive alcohol drinking among the alcohol dependent models when compared to control models that were not alcohol dependent. The researchers believe these observations suggest that during withdrawal the brain's stress system gets recruited and is responsible for a negative emotional state that drives compulsive alcohol drinking through a negatively reinforced mechanism. "In other words, what we know from the literature and was confirmed by this study is that the negative reinforced mechanism consists of the insurgence of anxiety during withdrawal (which we call "dark side") which in turn drives compulsive drinking as a form of paradoxical self-medication," explained co-corresponding author Pietro Cottone, PhD, associate professors of pharmacology and psychiatry at BUSM.

During withdrawal the alcohol-dependent models show increased levels of the stress neuropeptide PACAP selectively in the BNST, compared to control models. This observation led the researchers to administer an experimental drug that blocks the effects of PACAP directly into the BNST of both the alcohol-dependent model and the controls. "We found that this treatment was able to completely block both the high anxiety-like behavior and the compulsive ethanol drinking of ethanol-dependent models without affecting behavior in the control models," said co-corresponding author Valentina Sabino, PhD, associate professors of pharmacology and psychiatry at BUSM.

According to the researchers, these results provide further evidence that alcohol addiction, as many other forms of addictive disorders, is rooted in a negatively reinforced mechanism. "Compulsive alcohol drinking is mainly driven by a withdrawal-dependent negative emotional state. In this context, we found a new key player, PACAP, driving the negative reinforcing properties of alcohol and which can be targeted for the development of pharmacological therapies," added Cottone.
-end-
In addition to Sabino and Cottone, BUSM's Antonio Ferragud, PhD, Clara Velazquez-Sanchez, PhD and Margaret A. Minnig, BS, also contributed to this study

These findings appear online in the journal Neuropsychopharmacology.

Funding for this study was provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Boston University School of Medicine

Related Alcohol Articles from Brightsurf:

Alcohol use changed right after COVID-19 lockdown
One in four adults reported a change in alcohol use almost immediately after stay-at-home orders were issued: 14% reported drinking more alcohol and reported higher levels of stress and anxiety than those who did not drink and those whose use stayed the same.

Changes in hospitalizations for alcohol use disorder in US
Changes over nearly two decades in the rate of hospitalizations and in-hospital deaths from alcohol use disorder in the US were examined in this study.

Associations of alcohol consumption, alcohol-induced passing out with risk of dementia
The risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers was examined in this observational study with more than 131,000 adults.

New alcohol genes uncovered
Do you have what is known as problematic alcohol use?

Does estrogen influence alcohol use disorder?
A new study from researchers at the University of Illinois at Chicago shows that high estrogen levels may make alcohol more rewarding to female mice.

Sobering new data on drinking and driving: 15% of US alcohol-related motor vehicle fatalities involve alcohol under the legal limit
A new study in the American Journal of Preventive Medicine, published by Elsevier, found that motor vehicle crashes involving drivers with blood alcohol concentrations (BACs) below the legal limit of 0.08 percent accounted for 15% of alcohol-involved crash deaths in the United States.

Alcohol-induced deaths in US
National vital statistics data from 2000 to 2016 were used to examine how rates of alcohol-induced deaths (defined as those deaths due to alcohol consumption that could be avoided if alcohol weren't involved) have changed in the US and to compare the results by demographic groups including sex, race/ethnicity, age, socioeconomic status and geographic location.

Cuts in alcohol duty linked to 2000 more alcohol-related deaths in England
Government cuts to alcohol taxes have had dramatic consequences for public health, including nearly 2000 more alcohol-related deaths in England since 2012, according to new research from the University of Sheffield's School of Health and Related Research (ScHARR).

Integrated stepped alcohol treatment for people in HIV care improves both HIV & alcohol outcomes
Increasing the intensity of treatment for alcohol use disorder (AUD) over time improves alcohol-related outcomes among people with HIV, according to new clinical research supported by the National Institutes of Health.

The Lancet:Targets to reduce harmful alcohol use are likely to be missed as global alcohol intake increases
Increasing rates of alcohol use suggest that the world is not on track to achieve targets against harmful alcohol use, according to a study of 189 countries' alcohol intake between 1990-2017 and estimated intake up to 2030, published in The Lancet.

Read More: Alcohol News and Alcohol Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.