Peptide PACAP’s Key Role in Alcohol Addiction – Neuroscience News

Alcohol Addiction and Potential Treatment Target

Alcohol, the world’s most common addictive substance, has significant social, economic, and health consequences. In the United States alone, excessive alcohol use leads to $249 billion in annual costs and approximately 88,000 deaths. Despite its prevalence, alcohol use disorder remains under-treated, with limited pharmacological therapies available.

Key Facts:

1. Alcohol use disorder is a prevalent and under-treated condition with significant social and economic costs.
2. Chronic alcohol exposure leads to neuroadaptations in the brain, including the “bed nucleus of the stria terminalis” (BNST).
3. Researchers have identified pituitary adenylate cyclase activating polypeptide (PACAP) as a key factor in heavy alcohol drinking and a potential target for therapy.

A recent study conducted by researchers from Boston University Chobanian & Avedisian School of Medicine has shed light on the role of PACAP in alcohol addiction. The researchers found that PACAP, a peptide found in the BNST, is associated with heavy alcohol drinking and withdrawal.

In their experimental model, the researchers observed increased levels of PACAP in the BNST during withdrawal from heavy alcohol drinking. They also noted a similar increase in the levels of another stress neuropeptide called calcitonin gene-related peptide (CGRP). Both peptides have been implicated in stress and pain sensitivity, but their role in alcohol addiction is not well-established.

To further investigate the role of PACAP in alcohol addiction, the researchers used a virus in a transgenic model to block the neural pathways containing PACAP that specifically arrive at the BNST. They found that inhibiting PACAP significantly reduced heavy ethanol drinking.

These findings suggest that PACAP plays a crucial role in mediating the addictive properties of alcohol and could be targeted for the development of novel pharmacological therapies. The researchers believe that this discovery provides a potential avenue for improving the treatment of alcohol use disorder.

Sustainable Development Goals (SDGs)

• Goal 3: Good Health and Well-being – This research contributes to improving the understanding and treatment of alcohol addiction, ultimately promoting good health and well-being.
• Goal 9: Industry, Innovation, and Infrastructure – The identification of PACAP as a potential target for novel therapies highlights the importance of innovation in addressing public health challenges.
• Goal 17: Partnerships for the Goals – Collaboration between researchers, institutions, and organizations is essential in advancing knowledge and finding solutions to complex issues such as alcohol addiction.

Source: Boston University

About this Research

Author: Gina DiGravio

Source: Boston University

Contact: Gina DiGravio – Boston University

Image: The image is credited to Neuroscience News

Abstract

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by periods of heavy drinking and withdrawal. Chronic exposure to ethanol causes profound neuroadaptations in the extended amygdala, which cause allostatic changes promoting excessive drinking.

The bed nucleus of the stria terminalis (BNST), a brain region involved in both excessive drinking and anxiety-like behavior, shows particularly high levels of pituitary adenylate cyclase activating polypeptide (PACAP), a key mediator of the stress response.

Recently, a role for PACAP in withdrawal-induced alcohol drinking and anxiety-like behavior in alcohol-dependent rats has been proposed; whether the PACAP system of the BNST is also recruited in other models of alcohol addiction and whether it is of local or non-local origin is currently unknown.

Here, we show that PACAP immunoreactivity is increased selectively in the BNST of C57Bl/6J mice exposed to a chronic, intermittent access to ethanol.

While PAC1R expressing cells were unchanged by chronic alcohol, the levels of a peptide closely related to PACAP, the calcitonin gene related neuropeptide (CGRP), were found to also be increased in the BNST.

Finally, using a retrograde chemogenetic approach in PACAP-ires-Cre mice, we found that the inhibition of PACAP neuronal afferents to the BNST reduced heavy ethanol drinking.

Our data suggest that the PACAP system of the BNST is recruited by chronic, voluntary alcohol drinking in mice and that non-locally originating PACAP projections to the BNST regulate heavy alcohol intake, indicating that this system may represent a promising target for novel AUD therapies.

Funding: Funding for this study was provided by grants number AA026051, AA025038, and AA024439 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 Office of the Director of the National Institutes of Health (S10OD024993).

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