HDAC inhibitors may help regulate alcoholism-induced anxiety

Epigenetics is the study of changes in organisms caused by modifying gene expression - by alcohol, for example - rather than alteration of the genetic code itself. Recent evidence suggests that alcohol can inhibit activity of an enzyme called histone deacetylase (HDAC) in the amygdala, a brain region that is crucial for storing memories and regulating fear, anxiety, and other emotions. This presentation will address histone modifications in the rodent amygdala during chronic alcohol exposure and withdrawal.

"Current trends in the neuroscience field, particularly in alcohol research, indicate that drugs which are used to treat various types of cancer, such as HDAC inhibitors, appear to be very important in regulating brain function," said Subhash C. Pandey, Ph.D., professor and director of the Alcohol Research Center at the University of Illinois at Chicago. "The data presented in the symposium by me and other investigators, will clearly indicate that various kinds of HDAC inhibitors are important in regulating the anxiety that develops during alcohol withdrawal as well as alcohol intake. It might thereby be important in treating and preventing alcohol addiction." Pandey will present his research at the 39th Annual Research Society on Alcoholism in New Orleans June 25-29, 2016.

Pandey performed the experiments using an animal model during which rodents were exposed to alcohol for a long period of time. During a withdrawal period of 24 hours, one alcohol-exposed group was treated with an FDA-approved HDAC inhibitor called suberoylanilide hydroxamine (SAHA), also known as Vorinostat, followed by anxiety and epigenetic measures.

"We found that epigenetic mechanisms due to chemical modification of the histones and DNA appear to be very important in alcohol-related behaviors," said Pandey. "Our results indicate that specific types of HDACs are altered by chronic alcohol exposure; both in the adult brain and in the adolescent brain. HDAC-induced chromatin remodeling appears to be very important in regulating the anxiety-like behavior that appears during alcohol withdrawal, or the adolescent alcohol exposure-induced anxiety and drinking behavior at adulthood. These studies provide evidence that HDAC may serve as an important molecular mediator within the epigenome, thereby altering expression of synaptic plasticity-associated genes during alcoholism."

The good news, he added, is that HDAC inhibitors appear to correct deficits in histone acetylation. "Such drugs appear to be very crucial in preventing the comorbidity of anxiety and alcoholism," he said. "Our research has high potential for identifying HDACs as an important molecular target within the epigenome that can lead to the development of a new pharmacotherapy to treat or prevent alcoholism."