Protein links alcohol abuse and changes in brain's reward center

September 8, 2017 by Nicholas Weiler, University of California, San Francisco
Protein links alcohol abuse and changes in brain’s reward center
Credit: University of California, San Francisco

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 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 on a scientific level. Researchers still don't know how ethanol – a tiny molecule that, unlike all other drugs of , 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."

Previous 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 , an important part of the brain's reward circuitry, and that this increased mTORC1 activity is associated with alcohol-seeking. These findings suggested that mTORC1 might trigger structural changes in the nucleus accumbens that reinforce positive associations with alcohol, contributing to the cycle of excess drinking.

Earlier work from Ron's lab also found that blocking mTORC1 activity with rapamycin, a common immunity-suppressing drug, caused rodents to significantly cut down their drinking – without impacting their taste for other rewarding substances, such as sugar water. But because rapamycin has significant side effects, it is unsuitable to treat people with . In order to help in the search for new, more specific drugs to treat alcohol abuse, Ron's team wanted to better understand mTORC1's role in .

mTORC1's normal function is to promote the synthesis of new proteins, so in the new study, postdoctoral associate Sophie Laguesse, PhD, and her colleagues in the Ron lab used a technique called RNAseq to hunt new proteins that might be linked to mTORC1 activity in the in response to alcohol.

Of the 12 proteins they found, the researchers focused on one called prosapip1 – an earlier study had shown that it plays some role at synapses, although its specific function had not yet been identified. They found that that this protein changes the structure and activity of neurons in the nucleus accumbens after mice drank alcohol for a long time. When the authors genetically blocked the production of prosapip1, these alcohol-dependent changes were significantly reduced, and when offered a choice between alcohol and water, mice in which prosapip1 was blocked reduced their preference for alcohol.

This reduction in alcohol preference was quite specific: the mice's consumption of , normally very rewarding, was not affected by blocking the protein.

"We have identified a new protein that plays a crucial role in changing the landscape of neurons in the nucleus accumbens, which then leads to escalation of problem drinking," Ron said. "These findings open up research into the protein's role in neural plasticity, and also into how alcohol and other drugs of abuse alter our brains."

The findings plant mTORC1 and associated molecules firmly into neural pathways that allow drug abuse, and Ron hopes that future research will allow scientists to develop new, highly targeted approaches to treating the widespread scourge of addiction.

"I've been doing research on the molecular neurobiology of for many years and this is the first time I've seen a signaling molecule that appears to be shared by many drugs of abuse," Ron said. "I think in a way this may be a gateway to understanding drug addiction—it's a very exciting time."

Explore further: Resetting balance in reward centers may help treat alcohol addiction

Related Stories

Resetting balance in reward centers may help treat alcohol addiction

May 25, 2017
The human brain functions on a delicate balance of reinforcing positive behaviors and suppressing negative ones, which takes place in the dorsal striatum, a brain region critical for goal-directed behavior and implicated ...

Brain mechanisms in drug addiction—new brain pathways revealed

November 24, 2016
UNSW researchers have identified new brain pathways linked to addiction and shown that by manipulating them, drug seeking behaviour and motivation for alcohol can be reduced.

Why does prenatal alcohol exposure increase the likelihood of addiction?

July 7, 2017
One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are ...

Scientists identify promising target for development of new alcohol abuse medications

November 27, 2012
(Medical Xpress)—Decreasing the level of a key brain protein led to significantly less drinking and alcohol-seeking behavior in rats and mice that had been trained to drink, according to a study by researchers at the Ernest ...

Brain injury in kids might lead to alcohol abuse

August 14, 2017
Researchers at Ohio State University have surveyed previous studies to investigate the relationship between traumatic brain injuries and alcohol abuse. They found evidence that traumatic brain injuries in children and adolescents ...

Recommended for you

Exercise helps treat addiction by altering brain's dopamine system

May 28, 2018
New research by the University at Buffalo Research Institute on Addictions has identified a key mechanism in how aerobic exercise can help impact the brain in ways that may support treatment—and even prevention strategies—for ...

Warning labels on alcohol containers highly deficient, new research shows

May 21, 2018
Current health warning labels on alcohol beverage containers in New Zealand are highly deficient, new research from the University of Otago, Wellington shows.

Serving smaller alcoholic drinks could reduce the U.K.'s alcohol consumption

May 14, 2018
New research published in Addiction, conducted by researchers from the Universities of Liverpool and Sheffield, highlights the potential benefits of reducing the standard serving size of alcoholic beverages.

Anti-alcoholism drug shows promise in animal models

May 3, 2018
Scientists at The University of Texas at Austin have successfully tested in animals a drug that, they say, may one day help block the withdrawal symptoms and cravings that incessantly coax people with alcoholism to drink. ...

FDA-approved drugs to treat diabetes and obesity may reduce cocaine relapse and help addicted people break the habit

April 28, 2018
Cocaine and other drugs of abuse hijack the natural reward circuits in the brain. In part, that's why it's so hard to quit using these substances. Moreover, relapse rates hover between 40 and 60 percent, similar to rates ...

Buprenorphine may be safer than methadone if treatment duration is longer, study suggests

April 20, 2018
The less commonly prescribed opioid substitute buprenorphine may be safer than methadone for problem opioid users, especially if used during the first month of treatment, according to a study which includes University of ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.