Study Identifies Gene That Influences Alcohol Consumption in Mice

A new study has identified a gene variant engaged in communication among brain cells that directly influences alcohol consumption in mice.

However, the existence of such a gene variant, with similar effect on alcohol consumption in humans is still unknown.

The study was led by Csaba Vadasz, Ph.D., professor of psychiatric research in the department of psychiatry at New York University School of Medicine, and Director of the NeuroBehavioral Genetic Research Program at the Nathan Kline Institute in Orangeburg, N.Y.

It was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), and the U.S. Army.

The gene, known as Grm7, encodes a receptor subtype that inhibits the release of glutamate and other neurotransmitter molecules that brain cells use to communicate with one another.

The scientists recognized a gene variant, or polymorphism, that reduces the abundance of Grm7 messenger RNA (mRNA) in brain tissue. mRNA is the molecular intermediate between a gene and its protein product.

Mice that possess this gene variant consume more alcohol as compared to mice with higher brain levels of Grm7 mRNA.

“This is a noteworthy contribution, particularly since identifying genes that predispose to alcohol-related behaviors is such an arduous task,” said NIAAA Director Ting-Kai Li, M.D.

Scientists were aware for a long time now that a significant proportion of the risk for alcoholism is accounted to the genes.

However, the existence of multiple such genes that interact amongst themselves and with multiple environmental factors to influence drinking behavior has hampered studies aimed at isolating individual genes.

“Controlling for this background noise -- the various gene-gene and gene-environment interactions -- presents considerable methodological challenges,” indicated Dr. Csaba Vadasz.

In order to overcome these difficulties, the researchers applied a variety of genetic and analytic techniques to animals having nearly identical genetic background, but differing in their preference for alcohol, to identify a chromosomal region, and ultimately the Grm7 gene, associated with alcohol preference.

“Our findings support emerging evidence of the critical role that the brain’s glutamate pathways play in addiction,” said Dr. Vadasz.

He added: “While dopamine has traditionally been cast as a central actor in the neurochemistry of substance use and abuse, recent studies indicate that glutamate systems play an important role in reinforcement and addiction.”

The finding by Dr. Vadasz and colleagues may lead to new opportunities for developing drugs to treat alcohol dependence, in case, further studies reveal that a similar gene variant is relevant to alcohol problems in humans.

Dr. Vadasz speculated that these drugs might be designed to control the level of the Grm7 gene product or modulate the activity of the gene product itself.

A report of the study appears as an online Article in Press in Genomics.

Source-ANI
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