Yale Graduate School of Arts and Sciences

Graduate School News and Events

Exploring the Neurobiology of Alcoholism

Jacqueline Barker (Neuroscience) is part of a team of Yale researchers who are looking into the neurobiology of addictive behavior. By administering a simple behavioral test, they are able to predict which mice will later exhibit alcoholism-related behaviors such as the inability to stop seeking alcohol and a tendency to relapse.

The findings were published in the August 26 issue of the journal Nature Neuroscience and Jacqui was lead author of the article. Mary Torregrossa, an associate research scientist in psychiatry at the Medical School, was a co-author. The work was carried out in the lab of Jacqui's advisor Jane Taylor, the Charles B.G. Murphy Professor of Psychiatry and professor of psychology at the Yale School of Medicine.

The findings suggest that a similar test for people might be able to identify individuals who are at high risk of developing alcohol problems before they begin drinking.

“We are trying to understand the neurobiology underlying familial risk for alcoholism,” said Taylor, senior author of the study. “What is encouraging about this study is that we have identified both a behavioral indicator and a molecule that explains that risk.”

Many high school- and college-aged students abuse alcohol during their school years, but only a minority end up dependent upon alcohol later in life. While there is a clear genetic risk for alcoholism, not all children of alcoholics become dependent. Scientists have been busy trying to find ways to predict which adolescents are at greatest risk before drinking begins.

In a classic Pavlovian experiment, the Yale team found mice that reacted the most to a food cue also exhibited greater alcoholism-related behaviors. Importantly, the mice did not differ in other food-seeking behaviors. The researchers also identified a role for neural cell adhesion molecule (NCAM) and its modified form, PSA-NCAM, known to be involved in brain plasticity. Mice with low levels of PSA-NCAM in an area of the prefrontal cortex seemed unable to control their alcohol-seeking behavior, while the reward-seeking behavior of mice with higher levels of the molecule was more flexible and less indicative of addiction.

“This would make sense since alcoholism is associated with a lack of neurobiological and behavioral plasticity,” Taylor said. “The brains of alcoholics seem to get stuck in the same patterns of activity.”

These experiments compose a chapter of Jacqui’s thesis, and she has been responsible for carrying out the experiments and the data analysis. The interpretation of the results has been done together with her co-authors.

The rest of her thesis will continue to investigate “individual differences in the circuitry that mediates inflexible reward seeking and that may predict a propensity toward addictive behavior.” Using pharmacological and other tools, she is trying “to see if we can alter inflexible reward-seeking activities, in part to determine and assess a causal relationship. We believe this work will allow us to assess differences that exist prior to drug exposure that may predispose mice to addiction-related behavior. Understanding the mechanisms of learning and memory, and in particular the potentially maladaptive learning processes that underlie addiction, may enable the identification of new therapeutic strategies for the prevention and treatment of addictive disorders.”

This study is affiliated with the Yale Center for the Translational Neuroscience of Alcoholism and funded by the National Institutes of Health.

Jacqui earned her undergraduate degree from Ohio Wesleyan University.

Jacqueline Barker

Jacqueline Barker