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 28 May 2018

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News

Scientists identify brain mechanism that boosts response to alcohol

Neuroscientists at University of California San Francisco's Ernest Gallo Clinic and Research Center (EGCRC) have discovered a chemical reaction in the brain that maintains the urge to drink alcohol.

News image

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For years researchers have known that alcohol and all other addicting substances activate a brain region known as the nucleus accumbens, principally through the action of the neurotransmitter dopamine.

The study demonstrates how dopamine release in the brain may contribute to alcohol craving and drinking behavior.

The research shows that neurons in the nucleus accumbens may become hypersensitive to alcohol because a signaling molecule links two chemical pathways. One of these involves dopamine, and the other involves the neuromodulator adenosine.

This combined effect may be required to maintain the urge to drink alcohol, the scientists found.

Alcohol unleashes a "synergy" between the two chemical pathways via the signaling molecule, the researchers discovered.

Thus, this molecule may make a promising target for drugs to treat alcoholic cravings and excessive drinking.

The research is reported in the 14 June 2002 issue of the journal Cell.

The unexpected agent linking the two processes is known as a beta-gamma dimer, a signaling molecule in all cells.

Researchers already knew that alcohol triggers a series of chemical steps in neurons through the cell's adenosine receptor, leading to changes in gene activity.

What they discovered is that the beta-gamma dimer, released normally through the neuron's dopamine receptor, amplifies this adenosine pathway chemical cascade.

This boosts the brain's response to alcohol.

Beta-gamma dimer links the dopamine and adenosine chemical pathways.
UCSF

"Synergy is a most remarkable finding," said Ivan Diamond, Director of the EGCRC.

"It enables a substance taken into the body - alcohol - to team up with the normal, ongoing dopamine process to cause an exaggerated response to alcohol."

"We believe synergy causes hypersensitivity to alcohol in those neurons which have both dopamine and adenosine receptors, as in the nucleus accumbens.

"Most neurons in the brain do not have both receptors on the same cell and should not be as responsive to alcohol," he added.

"The other remarkable finding is that beta-gamma dimers are required for synergy and for voluntary alcohol consumption.

"This appears to be the first behavioral response regulated by beta-gamma dimers and provides a novel target for new medications to prevent or reduce excessive drinking," he concluded

"Today's report fast-forwards efforts to understand the precise brain mechanisms involved in alcohol-seeking behavior," said Raynard S. Kington, Acting Director of the National Institute on Alcohol Abuse and Alcoholism.

"Extending this work in animal and human studies may fast-forward the development of medications to impede alcohol-seeking behavior and prevent relapse in dependent drinkers."

UCSF
20 June 2002

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