A Molecular Mechanism Involved in Alcohol Preference

In a recent paper in Science, Waggoner Center researchers Dayne Mayfield and Sean Farris, and investigators from Linköping University in Sweden, uncovered a molecular mechanism involved in the preference for alcohol over other rewards.   Utilizing a procedure that arguably models alcohol addiction in rats, they found that a subset of rats self-administered alcohol even when a sweet, high-value reward was available.  These rats also showed high motivation to obtain alcohol and drink it despite negative consequences, such as foot shocks or when it was adulterated with quinine. 

In these animals, the amygdala – a brain region involved in emotion and memory – had a decreased amount of messenger RNA that encodes the protein GAT-3.  GAT-3 is important for reuptake of the brain’s chief inhibitory chemical messenger GABA after it is released from neurons.   Electrophysiological studies showed evidence of excess GABA outside cells in the amygdala of these rats, consistent with impairment of GABA transport function.   Suppressing levels of GAT-3 in the amygdala of rats selected for high saccharine intake generated an increased choice preference for alcohol over saccharine.  Postmortem samples of humans with alcohol dependence showed decreased messenger RNA for GAT-3 in the amygdala.

These findings suggest that impaired GABA transport in the amygdala is causally related to the development of addiction to alcohol.

Link to Scientific American article about this study:  https://www.scientificamerican.com/article/scientists-pinpoint-brain-region-that-may-be-center-of-alcohol-addiction/

Link to full Science paper:  http://science.sciencemag.org/content/sci/360/6395/1321.full.pdf