Center Line Newsletter

Volume 18, Number 1, March 2007

Director's Column

Dr. A. Leslie Morrow
Associate DirectorDirector, Bowles Center for Alcohol Studies

What a pleasure to write about the cutting edge work of Dr. Leslie Morrow. GABAA receptors are the major proteins responsible for the signaling of GABA, a critical inhibitory transmitter that is the major brake within the brain. The brain, in large part, works by selective inhibition. GABA regulates many intricacies of brain function that require selective inhibition. Examples of selective inhibition include focusing on a conversation in the presence of background noise or having that noise become the annoying focus of your attention. The ability to focus often depends on GABA inhibition of specific brain pathways.

GABA is very abundant and common across the brain, and if it isn’t working properly, it has the potential to cause seizures. But more subtly, it controls anxiety, mood and muscle tone, key elements of relaxation and health. Morrow’s lab has studied the unique configurations of GABAA subunits (each a gene) that make different subtypes of GABAA receptors across the brain. Further, she has found adaptive changes in the expression of types of complexes within neurons during chronic ethanol treatment and withdrawal. However, most exciting is Morrow’s recent discovery that ethanol regulates which GABAA receptor complexes become “active” cell surface receptors – an effect that appears to be key to understanding GABA neurotransmission. Several findings suggest that GABA is a central component of alcohol’s actions, and discoveries are of paramount importance for understanding GABA transmission and how it is altered by alcohol dependence. This work is nicely presented in the cover article. However, Morrow’s discoveries go far beyond alcoholism.

Anxiety and mood are key components of multiple mental disorders. Our mood and anxiety can make the glass half full or half empty. Most mental disorders occur much more often than expected by chance in alcohol abusing and alcohol dependent individuals, with dependent individuals even more likely than abusers to have mental disorders. Dysfunctional feelings can be crippling, and GABA contributes to those processes. The role of GABA in mental disease is likely to involve endogenous neurosteroids altering GABA in ways that make the brain dysfunctional. Loss of inhibitions and loss of control could involve loss of selectivity in GABA functions in the brain.

Morrow’s new discoveries provide an entirely new process regulating this critical component of brain function. Her work may lead to new therapies for alcoholism and many other mental afflictions. It continues to excite scientists across the world. We do all we can at UNC to support her continued efforts to understand mental disease and innovative new ideas on how it might be treated.