Medicine: Out in the Open

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If researchers could develop medical tests that identify biochemical signposts indicating a predisposition to alcoholism, they could warn potential alcoholics before trouble started. SUNY's Begleiter found just such a potential marker in the brain. By using an electroencephalogr aph to measure the brain waves of nondrinking sons of alcoholic fathers, Begleiter discovered that a particular brain wave called the P3 showed a dampened response. In each instance the sons' brain waves closely duplicated those of their fathers, while other subjects with no family history of alcoholism showed strong P3 waves. In addition, Dr. Marc Schuckit, a researcher at the San Diego Veterans Administration, has found that after several drinks some men whose fathers are alcoholics show fewer changes in the levels of two hormones, prolactin and cortisol, than men whose fathers are nonalcoholics. Eventually, such findings may provide important clues in the search for the genes involved in alcoholism.

Scientists acknowledge that work on the effects of alcohol on individual brain cells is still in its infancy. Part of the problem is that ethanol, the active ingredient in alcoholic drinks, easily penetrates the membranes of all cells and disrupts their normal function. Unlike other psychoactive drugs, ethanol does not target specific parts of nerve cells, or neurons, but seems to enter cell membranes and sabotage the nervous system indiscriminately.

Steven Paul, chief of the clinical neuroscience branch at the National Institute of Mental Health, is studying how ethanol affects certain cells in the brain to induce sedative effects. He is looking at a group of receptors, sites on the membranes of brain cells, that link with a molecule called gamma- aminobutyric acid (GABA), a neurotransmitter that moves across the synapses between neurons. GABA homes in on a complex known as the GABA-benzodiazepine receptor. If there are a sufficient number of GABA molecules present in certain areas of the brain, anxiety diminishes. Tranquilizers such as Valium and Librium work by attaching themselves to the receptor and increasing GABA's effectiveness.

Paul believes ethanol also reduces anxiety by acting on those GABA-sensitive neurons. Altering the amount of GABA in the brain could theoretically neutralize the effects of intoxication. To that end, Paul is currently experimenting with a drug, Ro15-4513, that blocks ethanol's ability to activate the GABA receptor, thus sharply reducing alcohol's sedative effects in rats. Although the drug is toxic to humans, variants could one day be useful in treatment. Other scientists are studying a new class of drugs that seem to block the alcoholic's craving for a drink. These compounds boost the amount of another neurotransmitter, serotonin, in the brain, thus encouraging a sense of well-being -- and bolstering abstinence.