Volume 21, Number 1, May 2010
Dr. Fulton T. Crews
Director, Bowles Center for Alcohol Studies
The biological factors that underlie alcohol-induced actions in brain are multifaceted and complex. Dr. Porcu’s studies on neuroactive steroids that are elevated by alcohol are at the cutting edge of factors that regulate the acute response to alcohol, which in part determines how much you drink. Although alterations in steroids have long been associated with alcohol abuse and other mental diseases, the role of neuroactive steroids has only recently been elucidated and new types of neuroactive steroids are continually being found. Porcu’s discoveries are notable in that she has both developed methods to measure neuroactive steroids and used these methods to establish principle compounds and responses to alcohol. Neurosteroids appear to regulate alcohol sedative responses. Studies have found that young individuals with a low sedative response to alcohol have a greater risk of becoming alcohol dependent in their lifetime. The increased risk is likely due to increased drinking, since sedated individuals will reduce their drinking. Understanding how neurosteroids impact responses to ethanol will contribute to understanding what regulates the quantity of alcohol people drink. Alcohol abuse, stress and steroid hormones converge on a variety of mental dysfunctions within unknown etiology. These studies will contribute to understanding the biological mechanisms that control acute alcohol intake and sensitivity to alcohol sedation.
The Hodge laboratory models drinking behavior and relapse drinking, a model of increased drinking following drinking experience followed by abstinence with a return to access to alcohol that results in a pronounced increase in drinking quantity and effort (lever pressing) to obtain alcohol. His discovery of MAP kinase activation during drinking following abstinence is a new target in his efforts to find medications useful for alcohol dependence. His earlier discoveries of mGLuR5 regulation of drinking behavior have exploded within the addiction community with large numbers of investigators currently studying this potential therapeutic target. The Hodge laboratory approach of identifying targets and then following with pharmacological interventions continues to define new and novel ways to reverse compulsive, excessive alcohol abuse. In time, these studies will improve efforts to treat and reverse excessive drinking