Photo by Logan Weaver | @LGNWVR on Unsplash.

Grant Award

Researchers Awarded $2.9M to Investigate Brain Mechanisms that Drive Alcohol Use Disorder

Hope is to identify potential new therapeutic targets for treatment.

Researchers Valentina Sabino, PhD, professor of pharmacology, physiology & biophysics and psychiatry, and Pietro Cottone, PhD, associate professor of pharmacology, physiology & biophysics and psychiatry, have received a $2.9M award from the NIH’s National Institute of Alcohol Abuse and Alcoholism to fund their five-year project, “The role of PACAP of the extended amygdala in heavy alcohol drinking.”

Our goal is to better understand how chronic alcohol exposure changes the brain’s stress circuitry.

Valentina Sabino, PhD

Alcohol use is widespread and alcohol use disorder (AUD) causes substantial harm. AUD affects 29 million individuals and causes more than 140,000 deaths annually in the U.S. alone. Individuals with AUD also often struggle with emotional distress and heightened pain sensitivity during withdrawal, which can further undermine recovery. Current drug options are limited, and only modestly effective, so more efficacious and better tolerated options are urgently needed.

Sabino and Cottone also co-direct BU’s Laboratory of Addictive Disorders. Their research focuses on understanding how stress-related brain systems contribute to compulsive alcohol drinking, anxiety and relapse.

The newly funded project will study a brain signaling system involving pituitary adenylate cyclase-activating polypeptide (PACAP), a molecule that plays an important role in the body’s stress response. The researchers will investigate how PACAP activity in a brain region known as the bed nucleus of the stria terminalis (BNST) may be a driver of excessive alcohol drinking, anxiety-like behaviors and increased sensitivity to pain associated with alcohol addiction.

“Our goal is to better understand how chronic alcohol exposure changes the brain’s stress circuitry,” said Sabino. “By identifying the molecular and neural mechanisms involved, we hope to uncover new pathways that could then lead to more effective treatments for alcohol use disorder.”

The team will use advanced neuroscience approaches, including pharmacological, molecular, and viral techniques combined with well-established animal models of alcohol dependence and stress-related behaviors. The project also will examine how PACAP interacts with corticotropin-releasing factor (CRF), another key stress-related signaling system in the brain.

This work will allow us to dissect specific neural circuits that may underlie compulsive drinking and the negative emotional states that accompany addiction

Pietro Cottone, PhD

“Stress systems in the brain are increasingly recognized as central drivers of addiction,” said Cottone. “This work will allow us to dissect specific neural circuits that may underlie compulsive drinking and the negative emotional states that accompany addiction.”

According to the investigators, the findings could help advance the development of novel medications targeting stress-related neuropeptide systems involved in alcohol addiction and related psychiatric symptoms.