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Found: a novel assembly line in brain whose product may prevent alcoholism

alcohol silhouette

High-functioning binge drinkers can seem charming and stylish. The ultimate case in point: Nick and Nora of the famed Thirties/Forties "Thin Man" film series (you can skip the ad after the first few seconds).

But alcoholism's terrific toll is better sighted on city streets than in celluloid skyscraper scenarios. At least half of all homeless people suffer from dependence on one or another addictive drug. (My Stanford Medicine article "The Neuroscience of Need" explores the physiology of addiction.) Alcohol, the most commonly abused of them all (not counting nicotine), has proved to be a particularly hard one to shake.

"Alcoholism is an immense national and international health problem," I wrote the other day in a news release explaining an exciting step toward a possible cure:

More than 200 million people globally, including 18 million Americans, suffer from it. Binge drinking [roughly four drinks in a single session for a man, five for a woman] substantially increases the likelihood of developing alcoholism. As many as one in four American adults report having engaged in binge drinking in the past month.

While there are a few approved drugs that induce great discomfort when a person uses them drinks alcohol, reduce its pleasant effects, or alleviate some of its unpleasant ones, there's as of yet no "magic bullet" medication that eliminates the powerful cravings driving the addictive behavior to begin with.

But a study, just published in Science, by Stanford neuroscientist Jun Ding, PhD, and his associates, may be holding the ticket to such a medication. In the study, Ding's team identified a previously unknown biochemical assembly line, in a network of nerve cells strongly tied to addiction, that produces a substance whose effect appears to prevent pleasurable activity from becoming addictive. The substance, known as GABA, acts as a brake on downstream nerve-cell transmission.

In experiments with mice, the researchers showed that binge-drinking shuts down this assembly line. So does a cluster of genetic mutations already known to be associated with alcoholism. The study also demonstrated that specifically restoring  GABA levels, by tweaking this just-unearthed production line in the addiction-fueling nerve cells, prevents an otherwise prominent turn toward alcohol preference and consumption in mice who've undergone the murine equivalent of the Nick-and-Nora experience.

GABA is hugely important and mightily abundant throughout the brain. But in almost the entirety of that organ it's produced by a different assembly line employing other components and steps. In contrast, the novel, "alternative" assembly line looks to be situated only in the very nerve cells that, absent GABA's braking action, fuel addiction. So a drug that souped up the alternative GABA assembly line without inducing the chemical's overproduction the rest of the brain  (which could be as disastrous as an overdose of Valium or similar drugs) could someday turn out to be just the magic bullet that shoots down addiction by shutting down the craving for  alcohol - and, it may turn out, cocaine, morphine, and even gambling or compulsive email checking.

Previously: Alcohol: Not just a man's problem, The trial: My Kafkaesque dance with dopamine and Better than the real thing: How drugs hot wire our brains' reward circuitry
Photo by Stuart Richards

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