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Scientists identify brain mechanism that boosts response to alcohol

Neuroscientists at UCSFs Ernest Gallo Clinic and Research Center (EGCRC) have discovered that a molecule in neurons boosts the brains response to alcohol, triggering in minutes chemical changes that maintain an urge to drink alcohol. Blocking the molecules action might prevent excessive drinking, they conclude.

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 involving dopamine, and the other involving 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, so this molecule may make a promising target for drugs to treat alcoholic cravings and excessive drinking.

The research is reported in the June 14 issue of the journal CELL. The paper describes new discoveries in rat neuron cell cultures that were confirmed in studies of alcohol consumption in rats.

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 cells adenosine receptor, leading to changes in gene activity. What they discovered is that the Beta-gamma dimer released normally through the neurons dopamine receptor, amplifies this adenosine pathway chemical cascade. This boosts the brains response to alcohol.

"Synergy is a most remarkable finding," said Ivan Diamond, MD, PhD, UCSF professor of neu
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
13-Jun-2002


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