The National Institute on Alcohol Abuse and Alcoholism has awarded $2.6 million to Alex M. Dopico, MD, PhD, Van Vleet Chair of Excellence and professor in the Department of Pharmacology, Addiction Science, and Toxicology (PHAST) at the University of Tennessee Health Science Center, to study cerebrovascular dysfunction that could contribute to alcohol-induced blackouts.
Alcohol-induced blackouts are a form of amnesia caused when a person drinks heavily enough to temporarily block the transfer of memories from short- to long-term storage — known as memory consolidation — in the brain’s hippocampus. These blackouts can occur in anyone who heavily drinks within a short period, regardless of age, education, socioeconomic status, drinking history, sex, or sexual orientation. A serious consequence of alcohol misuse, alcohol-induced blackouts drastically increase the risk for dangerous behaviors, injuries, and other harms.
Previous studies have sought the cellular basis of alcohol-induced blackouts, focusing primarily on neuronal or glial elements. Dr. Dopico’s study departs from all previous research by focusing instead on blood perfusion of this brain region. His project builds on his years of research and his discovery of a molecular site in BK channel protein receptors where alcohol is recognized and interacts to make cerebral arteries contract.
Dr. Dopico’s team, including Anna Bukiya, PhD, and Brendan Tunstall, PhD, both faculty in the PHAST department, will explore how, at concentrations reached in the brain during alcohol-induced blackouts, these amino acids cause artery constriction, regional hippocampal ischemia, and ultimately, blackouts. The team will use a wide array of methodologies, from computational models of alcohol-BK receptor interaction to behavioral testing in animal models. They aim to fully characterize the vascular target for alcohol, the first step in designing drugs to counteract alcohol-induced blackouts. They will examine whether there is a difference between the biological sexes in how the target responds to alcohol action. Finally, they will test the effectiveness of their newly discovered vasomodulator as a possible treatment.
“As recently done in other fields within the neurosciences, such as neurodegeneration, cognition deficits, and dementia, we are bringing a vascular component(s) as central to the pathophysiology of substance use disorders, alcohol-induced blackouts in particular,” Dr. Dopico said.