Alcohol Abuse Decreases Brain’s Capacity to ‘Extinguish’ Fearful Memories

2010 NARSAD Young Investigator Grantee, Thomas L. Kash, Ph.D., of the University of North Carolina, Chapel Hill, expert on anxiety and other disorders
Thomas L. Kash, Ph.D.

From The Quarterly, Fall 2012

Alcoholism and anxiety disorders are not only among the most common brain and behavior disorders; frequently, they occur in the same individuals. The leading theories about their co-occurrence “emphasize anxiety symptoms arising as a result of a history of heavy drinking,” notes 2010 NARSAD Young Investigator Grantee, Thomas L. Kash, Ph.D., of the University of North Carolina, Chapel Hill.

In recent research published in Nature Neuroscience (September 2012), Dr. Kash and a team of co-investigators found something different: chronic abuse of alcohol makes it more likely that a person who is subject to trauma will not be able to ‘extinguish’ their memories of the traumatic event. This is a primary symptom of post-traumatic stress disorder (PTSD): the sufferer is revisited by the fear experienced during the traumatic event long after the danger has passed.

Over a month’s time the scientists regularly exposed one group of mice to amounts of alcohol equivalent to twice the legal driving limit. A second group of mice received no alcohol. Both groups were then trained to fear a sound that was associated with an uncomfortable shock. But after a time, the shocks were discontinued and the mice were only exposed to the “associated” sound. The mice that had not been chronically exposed to alcohol had no problem extinguishing their fear of the tone once the shocks were discontinued. Not so for the ‘alcoholic’ mice, which froze in their tracks whenever the sound was played, even long after the shocks stopped.

The researchers connected these behavioral observations with actual changes in brain circuitry. The brain pathway involved in the extinction of fearful memories has been previously identified in research, leading this team to track specific activity there in both sets of mice. They were able to connect the impairment of fear extinction in the alcohol-exposed mice with both the shape of the neural arbor—the branching connections sent out by neurons—in the prefrontal cortex, and with changes in NMDA (N-methyl-D-aspartate) receptors. NMDA receptors are thought to be critical in synaptic plasticity and essential to learning and memory.

The team was able, therefore, not only to see that alcohol has detrimental effects on the natural capacity to extinguish fearful memories, but was also able to offer insight into how this happens. Our research “implies that a chronic history of alcohol abuse may increase the risk of persistent fear after psychological trauma,” Dr. Kash and his team write in their research paper.

This finding pinpoints a specific place in the brain where alcohol causes damage leading to problems overcoming fear, thus opening the door to the discovery of new methods of preventing the pathology from occurring. Also involved in this study were 2005 NARSAD Young Investigator Grantee, Andrew Holmes, Ph.D., of the National Institute on Alcohol Abuse & Alcoholism (NIAAA/NIH), and 2003 NARSAD Young Investigator Grantee, Paul B. Fitzgerald, Ph.D., of Monash University.