Research Highlights

Research News
Friday, February 5, 2016
Author:

The concept of addiction as a brain disease is still being questioned. Yet, an article published in The New England Journal of Medicine by NIDA Director Dr. Nora Volkow, NIAAA Director Dr. George Koob, and Dr. A. Thomas McLellan, co-founder and Chair of the Board of the Treatment Research Institute, further enforces this concept. The review article summarizes recent scientific advances in the neurobiology of addiction....

Read the announcement at https://www.drugabuse.gov/news-events/news-releases/2016/01/review-artic....

 

 

Research News
Friday, February 27, 2015
Author: Gregory Roa

Researchers led by Catherine Fortier at Harvard Medical School found that chronic alcohol misuse damaged white matter in areas of the brain that are important for self-control and recovery from alcoholism. The findings appeared in the December 2014 issue of Alcoholism: Clinical & Experimental Research.

Using high-resolution diffusion magnetic resonance brain scans, the researchers compared a group of 20 healthy light drinkers to a group of 31 individuals with a history of alcoholism. The recovering alcoholics drank heavily for an average of 25 years and had been sober for about five years.

Compared with the light drinkers, the abstinent alcoholics showed pronounced reductions in the structural integrity of frontal and superior white matter tracts. According to the authors, the results suggest altered connectivity in frontostriatal circuits—pathways associated with the amygdala, hippocampus, nucleus accumbens, regions that are involved in the brain’s reward system. These networks are essential for controlling impulsive behavior and stopping drinking.

The study also found that longer and heavier alcohol abuse was associated with greater damage. The findings pointed to possible recovery of white matter tissue in drinkers who became abstinent before they turned 50 years of age. 

The authors recommend that future investigations should continue to explore white matter changes due to alcohol misuse, including measurements related to the severity of alcoholism and questions about tissue recovery with maintained abstinence.

Brain images

 

 

 

 

 

 

 

Image Caption: Brain images from the study; used with permission. Credit: Dr. Catherine Fortier, Harvard Medical School.

Adapted from the story published in the NIAAA Spectrum, February 2015, Volume 7, Issue 1.

 

 

Research News
Monday, March 31, 2014
Author: Erin Bryant

Results from a recent NIAAA study suggest that the medication ibudilast may be viable as a potential treatment for alcohol dependence. Ibudilast, an anti-inflammatory medication that acts as a non-selective phosphodiesterase inhibitor, reduces alcohol drinking and relapse in alcohol-preferring P rats, high-alcohol drinking HAD1 rats, and in mice made dependent on alcohol through cycles of alcohol vapor exposure.

Neuroinflammatory signaling pathways in the central nervous system are of current interest as potential pharmacotherapy targets for alcohol dependence. When administered twice daily, ibudilast reduced alcohol drinking in rats by approximately 50% and reduced drinking by alcohol-dependent mice at doses which had no effect in non-dependent mice.

Research News
Monday, March 31, 2014
Author: Erin Bryant

Alcohol produces a wide range of pharmacological effects on the nervous system through its actions on ion channels. The molecular mechanism underlying ethanol modulation of ion channels is poorly understood. NIAAA scientists used a unique method of alcohol-tagging to demonstrate that alcohol activation of a G-protein-gated inwardly rectifying potassium (GIRK or Kir3) channel is mediated by a defined alcohol pocket through changes in affinity for the membrane phospholipid signaling molecule phosphatidylinositol 4,5-bisphosphate.

Surprisingly, hydrophobicity and size, but not the canonical hydroxyl, were important determinants of alcohol-dependent activation. Altering levels of G protein Gβγ subunits, conversely, did not affect alcohol-dependent activation, suggesting a fundamental distinction between receptor and alcohol gating of GIRK channels. The chemical properties of the alcohol pocket revealed here might extend to other alcohol-sensitive proteins, revealing a unique protein microdomain for targeting alcohol-selective therapeutics in the treatment of alcoholism and addiction. Understanding this mechanism will be critical for developing alcohol-selective therapeutics that can perhaps prevent alcohol abuse and treat addiction.

Research News
Monday, March 31, 2014
Author: Erin Bryant

A recent NIAAA study determined the expression profile of microRNAs (miRNAs) in the nucleus accumbens (NAc) of rats treated with alcohol. MicroRNAs are non-coding RNA molecules thought to play a key role in and the regulation of gene expression. The study results suggest that multiple miRNAs were aberrantly expressed in rat NAc after alcohol injection. Among them, miR-382 was down-regulated in alcohol-treated rats.

In both cultured neuronal cells in vitro and in the NAc in vivo, researchers identified that the dopamine receptor D1 (Drd1) is a direct target gene of miR-382. Via this target gene, miR-382 strongly modulated the expression of DeltaFosB. Moreover, overexpression of miR-382 significantly attenuated alcohol-induced up-regulation of DRD1 and DeltaFosB, decreased voluntary intake of and preference for alcohol and inhibited the DRD1-induced action potential responses. The results indicate that miRNAs are involved in and may represent novel therapeutic targets for alcoholism.

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