With April being Alcohol Awareness Month, we sat down with David A. Kareken, PhD, director of the Indiana Alcohol Research Center, to discuss work being done at the center, his own career and role as director, and some of his proudest achievements with the center.
Q: Tell me about the work that goes on at the Indiana Alcohol Research Center (basic overview)
The Indiana Alcohol Research Center (ARC) began in 1987 with its founding Director, Dr. Ting-Kai “T.-K.” Li, a Distinguished Professor at Indiana University who later served as the Director of the National Institute of Alcohol and Alcoholism (NIAAA) at the NIH. From its inception, the ARC has studied the genetic and environmental risks for developing alcohol use disorder (AUD).
The ARC has always had a very multi-disciplinary character, bringing together scientists who study the genetic, behavioral, and neurobiological mechanisms for AUD in both animal models and humans.
Q: How did you get started at the center?
My original research interests were in Alzheimer disease, specifically in understanding how the olfactory system might reflect early neurodegeneration. At the time, I was helping a colleague in the ARC, Dr. Sean O’Connor, who shared my interest in leveraging what was then the emerging technology of functional neuroimaging. T.-K. Li provided the specific intellectual “spark” that set me down the path of my own work in alcohol research.
The collaborative and translational spirit of the ARC kept me in the group and showed to me the importance of an interdisciplinary team in answering complex questions about the brain, motivated behavior, and the ways in which they can become maladaptive.
Q: What does your work as director entail?
The ARC director coordinates the Center’s activities and scientific agenda, and helps keep the scientific projects on track, with significant input from the Deputy (Cris Czachowski, PhD, Psychology, IUI) and Scientific (Chris Lapish, PhD, Anatomy, Cell biology & Physiology) Directors.
Q: What are the center’s research priorities?
The ARC has long prioritized a translational approach to studying inherited risk for AUD, with human investigations grounding the animal research, and mechanistic work in rodents informing human studies about effects related to a family history of AUD. To model family history in rodents, our Center investigators developed lines of rodents bred for high alcohol preference—a core resource now maintained by Nick Grahame, PhD (Psychology, IUI).
In human research, the Center is also known for its development of an intravenous alcohol infusion method to precisely control brain exposure to alcohol, eliminating the confounds related to individual variation in alcohol pharmacokinetics. First developed by Sean O’Connor, MD (Psychiatry), this resource is now maintained and refined further by Martin Plawecki, MD, PhD (Psychiatry).
Q: What work is currently ongoing at the center?
Our specific Center “theme” changes across the funding cycles, with past themes involving aspects of impulsivity and compulsivity in AUD risk. Given the rising prevalence of binge drinking, we are now studying inherited and acquired behavioral and neurobiological vulnerabilities that predispose individuals to more intense patterns of drinking.
In each of the three animal research components, and in the one human research component, we are using the tools that we’ve developed to understand how brain circuits work to sustain early intense drinking patterns.
Q: What are some of your proudest achievements during your time with the center?
Working closely with the Center, my research lab was the first to demonstrate that alcohol’s flavors, alone and absent intoxication, were sufficient to provoke dopamine transmission in the human reward system. Moreover, we showed that this dopaminergic response was greatest in those with a family history of AUD, suggesting that inherited factors might sensitize the brain’s reward system to cues that reflect alcohol’s presence.
Working with our collaborating Center colleagues at Purdue University (led by Joaquin Goñi, PhD), we demonstrated that those with a family history of AUD may have less reconfiguration in functional brain connectivity when transitioning between mental states— work that we continue to pursue. Most recently, we showed that the brain’s response to a natural reward— intense sweet taste— induces brain activity in nodes of the brain’s “salience” (sensory importance) network that predicts the subjective enjoyment of alcohol.
On a personal level, it’s been immensely gratifying to shepherd the ARC through its last two rounds of competitive renewal at the NIH to enable our investigators to conduct their work. The most enjoyable aspect of my position has been to work with this collegial multidisciplinary team. Having started my career as a clinical neuropsychologist, it seems an improbable journey that began by happenstance. I was also very lucky to have the close collaboration of a skilled methodologist, Mario Dzemidzic, PhD, and to have been mentored by people like Sean O’Connor (Psychiatry), and T.-K. Li, David Crabb and Jan Froehlich, PhD (Medicine). Ultimately, work like this is always a team effort.
