According to the results of a recent NIAAA-funded animal study, carrying a gene variant that affects the release of a specific brain protein may increase the risk of developing an alcohol use disorder. The protein, brain-derived neurotrophic factor (BDNF), affects the survival of existing neurons and the growth of new neurons and synapses, the junctures through which cell-to-cell communication occurs.

In the study, researchers tested the role of BDNF in alcohol addiction by creating a “knock-in” mouse carrying a gene that reduces activity-dependent BDNF release. These “knock-in” mice drank more alcohol, even when the alcohol was treated with bitter-tasting quinine. This suggests carriers of the variant gene compulsively drink alcohol despite negative results. The effect of the genetic mutation seemed to be specific to alcohol consumption because the mice’s consumption of other fluids did not change, nor was there any difference in their levels of anxiety or compulsive behaviors.

By increasing levels of BDNF in the ventromedial portion of the prefrontal cortex, a brain region involved in compulsive drug and alcohol seeking, the researchers were able to return the mice to moderate levels of alcohol intake. In addition, by administering a pharmaceutical compound (LM22A-4) developed to mimic the action of BDNF, researchers were able to put a stop to compulsive drinking behaviors. LM22A-4 appears to reduce compulsive alcohol-drinking without a generalized effect on motivation and may have potential as a therapeutic for humans.


Warnault, V.; Darcq, E.; Morisot, N.; Phamluong, K.; Wilbrecht, L.; Massa, S.M.; Longo, F.M.; and Ron, D. The BDNF valine 68 to methionine polymorphism increases compulsive alcohol drinking in mice that is reversed by tropomyosin receptor kinase B activation. Biological Psychiatry, June 12, 2015. [Epub ahead of print]. PMID: 26204799



Reprinted from the NIAAA Spectrum, Volume 7, Issue 3, September 2015.