Scripps Research Institute Study Links Brain Protein to Binge Drinking

By John Lavitt 07/20/15

Binge drinking is defined by heavy consumption of alcohol over a short period of time in order to reach intoxication.

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Scientists at the Scripps Research Institute have discovered the key role a brain protein plays in controlling binge drinking. When they deleted the gene for this protein in mice, it ramped up the alcohol consumption of the rodents and prevented the brain from signaling the rewarding properties of alcohol.

Published in the journal Proceedings of the National Academy of Sciences, the study could play a major role in the development of medications and medical procedures to address binge drinking behaviors in alcoholics.

Characterized by heavy episodic drinking, binge drinking is defined by heavy consumption of alcohol over a short period of time in order to reach the point of intoxication. According to the U.S. Centers for Disease Control and Prevention, binge drinking puts people at greater risk for health problems such as cardiovascular disease, liver disease, and neurological damage.

"Alcohol hits a lot of different targets in our brain, which makes disentangling the in vivo effects of alcohol quite complicated," explains TSRI biologist Candice Contet, senior author of the study. "Our study sheds light on the molecular mechanisms implicated in binge drinking."

The goal of the new study was to identify the role of a member of the "G protein-gated inwardly rectifying potassium channel" (GIRK) family in the behavioral and cellular responses to alcohol.

Distributed throughout the nervous system, GIRK channels decrease the excitability of neurons, making them less likely to fire. Alcohol can directly activate GIRK channels. Scientists did not know, however, whether this action was directly connected to the behavioral effects of alcohol.

In the new study, Dr. Contet and her colleagues decided to focus on the GIRK3 subunit, which had previously been shown to modulate the effects of other drugs, such as the "date rape drug" γ-hydroxybutyrate (GHB) and cocaine. The researchers investigated how GIRK3 influenced mouse behavior and neuronal function in the presence of alcohol. To do so, they compared "knockout" mice missing GIRK3 with normal mice.

GIRK3 knockout mice and controls showed differences in alcohol intake in a test mirroring human behavior during a "happy hour" at a bar. In this test, mice were given access to ethanol for only two hours a day, at a time when they were most likely to drink to the point of intoxication. The researchers found that GIRK3 knockout mice consumed much more alcohol than the control group.

"Mice lacking GIRK3 ... (are) drinking more because they feel less pleasure and therefore need to drink more to reach the same level of pleasure as normal mice," explained Contet.

A striking difference between normal and GIRK3 knockout mice emerged in the presence of alcohol. The pleasure pathway became completely insensitive to alcohol's activating effect without GIRK3. Alcohol also was unable to trigger the release of dopamine in the ventral striatum of GIRK3 knockout mice. The results suggest that GIRK3 knockout mice drink more ethanol to boost the engagement of other neural pathways mediating alcohol's rewarding effects.

"The dramatic effect of GIRK3 deletion on the ability of alcohol to excite VTA neurons was surprising. Even when applied at a very high concentration, alcohol was unable to alter the firing of neurons missing GIRK3," said research associate Melissa Herman.

The results of the study have led the researchers to believe that a compound selectively targeting GIRK3-containing channels could prove to be an effective treatment technique. Such a compound may hold promise for reducing alcohol consumption in heavy binge drinkers.

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Growing up in Manhattan as a stutterer, John Lavitt discovered that writing was the best way to express himself when the words would not come. After graduating with honors from Brown University, he lived on the Greek island of Patmos, studying with his mentor, the late American poet Robert Lax. As a writer, John’s published work includes three articles in Chicken Soup For The Soul volumes and poems in multiple poetry journals and compilations. Active in recovery, John has been the Treatment Professional News Editor for The Fix. Since 2015, he has published over 500 articles on the addiction and recovery news website. Today, he lives in Los Angeles with his beautiful wife, trying his best to be happy and creative. Find John on Facebook, Twitter, and LinkedIn.

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