Scientists find biological mechanism during transition to alcohol management

A team of Scripps Research Institute scientists has found a key biological mechanism underpinning the transition to alcohol dependence. This finding opens the door to the development of drugs to manage excessive alcohol consumption.

"Our focus in this study, like much of our lab's research, was to examine the role of the brain's stress system in compulsive alcohol drinking driven by the aversive aspects of alcohol withdrawal," said Scripps Research Associate Professor Marisa Roberto, Ph.D., senior author of the study.

"A major goal for this study," added research associate Nicholas Gilpin, Ph.D., the paper's first author, "was to determine the neural circuitry that mediates the transition to alcohol dependence."

In the new research, published in the 1 June 2011 issue of the journal Biological Psychiatry, the Scripps Research scientists demonstrated the key role of a receptor - a structure that binds substances, triggering certain biological effects - for neuropeptide Y in a part of the brain known as the central amygdala. The amygdala, a group of nuclei deep within the medial temporal lobes, performs an important role in the processing and memory of emotional reactions.

"We've known for quite some time that neuropeptide Y is an endogenous [naturally occurring] anti-stress agent," says Markus Heilig, clinical director of the National Institute of Alcohol Abuse and Alcoholism (NIAAA). "We've also known that development of alcohol dependence gives rise to increased sensitivity to stress. This paper elegantly and logically brings these two lines of research together. It supports the idea that strengthening neuropeptide Y transmission in the amygdala would be an attractive treatment for alcoholism. The challenge remains to develop clinically useful medications based on this principle."

Discovering the circuitry
Building on Gilpin's previous work on neuropeptide Y, in the new project, Gilpin, Roberto, and colleagues observed the effects of the administration neuropeptide Y in the central amygdala on alcohol drinking in rats. Alcohol-dependent rats were allowed to press levers for ethanol and water during daily withdrawal from chronic alcohol exposure.