Protein Links Alcohol Abuse and Changes in Brain’s Reward Center

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When given access to alcohol, over time mice develop a pattern similar to what we would call “problem drinking” in people, but the brain mechanisms that drive this shift have been unclear. Now a team of UC San Francisco researchers has identified a protein that links alcohol consumption with structural changes in one of the “reward centers” in the mouse brain.

The work, published online Sept. 7, 2017, in Neuron, casts new light on the molecular domino effect by which alcohol triggers long-lasting changes in brain cells that drive heavy drinking, the scientists said.

Though it is legal and easily obtained, alcohol remains an unusual and mysterious drug on a scientific level. Researchers still don’t know how ethanol – a tiny molecule that, unlike all other drugs of abuse, does not have a specific site of action – can alter brain function to promote compulsive, uncontrolled consumption and alcohol-seeking despite negative consequences.

“There is – rightfully – a lot of media attention right now on opiate abuse and addiction,” said Dorit Ron, PhD, professor and Endowed Chair in Cell Biology of Addiction in UCSF’s Department of Neurology, and the new study’s senior author. “But alcohol abuse and addiction are much bigger problems, and the human cost is staggering: 3.3 million people die every year in the world from alcohol abuse. Unfortunately, there are only a few medications on the market to reduce craving and relapse, and none of them work very well.”

Dorit Ron, PhDPrevious work in rodents by the Ron lab and others has suggested that a protein by the name of mTORC1 may be a key mediator of addiction to multiple drugs of abuse, including cocaine, morphine and alcohol. In earlier studies, her lab has shown that excessive drinking boosts mTORC1 activity in the nucleus accumbens, an important part of the brain’s reward circuitry, and that this increased mTORC1 activity is …

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