IUPUI researchers awarded grant to study how brain's reward system is hijacked by alcohol

With the support of a $545,000 three-year grant from the National Institute on Alcohol Abuse and Alcoholism, researchers from the School of Science at Indiana University-Purdue University Indianapolis are conducting research on how the brain's reward system -- the circuitry that helps regulate the body's ability to feel pleasure -- is hijacked by alcohol.

Scientists have only a rudimentary understanding of how alcohol affects neurons in the brain. It is known that, as any addictive drug, alcohol directly or indirectly acts on a specific population of brain cells, called dopamine neurons. Through this action, the neurotransmitter dopamine is released, which evokes feelings of pleasure. However, the biological mechanisms of how alcohol evokes dopamine release have not been determined; exploring this question is the major goal of the grant.

The synergistic approach of the IUPUI researchers -- biomathematician Alexey Kuznetsov, Ph.D., associate professor of mathematical sciences, and neuroscientist Christopher Lapish, Ph.D., assistant professor of psychology -- is novel as they marry the cutting-edge tools of mathematical modeling developed by Kuznetsov and the sophisticated experimental neuroscience experiments designed and conducted by Lapish to study the electrical properties that determine the release of the neurotransmitter dopamine in the brain. As a starting point, they are focusing on the brain's initial exposure to alcohol.

Kuznetsov has developed unique mathematical models as he homes in on why and how much dopamine is released when alcohol is consumed. With the same goal, Lapish is employing sophisticated tools and methods to measure and analyze electrical signals of dopamine neurons in rats. This synergy forms a two-way street with data from the recordings of the electrical impulses of the rat brains affecting how the mathematical models are constructed and the predictions generated by the mathematical models informing the study of the animal brains.

IUPUI undergraduates and graduate students are assisting the investigators in their work.

"Our mathematical models go much further than simple logic," Kuznetsov said. "What we are learning from experiments is critical. The direct connection of modeling and experiments enables us to test and refine our hypotheses."

"As we begin our second year on this project we are gaining a better understanding of how the brain responds to alcohol," Lapish said. "The cross talk between us drives this hypothesis-driven research. There are many unknowns to explore and interpret."

The IUPUI researchers are also collaborating with French scientists. "We are working on the problem at different levels -- we are modeling and studying the brains of live rodents -- in vivo work -- and they [the French researchers] are studying in vitro brain slices in the lab," Kuznetsov added.

"Alcohol addiction is among America's largest public health concerns yet we know far less about it than most other addictions. If we are going to successfully treat alcohol addiction we need to begin with the basics and understand how alcohol directly acts on dopamine neurons in both the alcoholic and normal brain," Lapish said.