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Some people react to stress by reaching for a few too many drinks. Now scientists may have uncovered the genetic basis for this impulse in a study conducted on mice. The root of the problem may lie in a glitch in a signaling network in the brain--the so-called CRH system--that regulates hormonal and behavioral responses to tension, according to a paper published today in the journal Science. Specifically, the gene CRH1, which makes a key receptor in this neural signaling process, appears to be the culprit. After extended periods of stress, mice lacking functional CRH1 receptors increased their alcohol intake. Normal mice, in contrast, showed no change in consumption. If applicable to humans, these results could have important treatment implications.
Initially the two groups of mice in the experiment exhibited similar drinking habits. Offered a choice between normal water and several solutions with different concentrations of alcohol, the mice chose an 8 percent solution. With this established, Rainer Spanagel of the Max Planck Institute of Psychiatry in Munich, Germany, and his colleagues then exposed the subjects to high-pressure situations, including attack by an unfamiliar mouse, to examine how stress altered their preferences. At first neither group changed. Prolonged periods of tension, however, led the mutant mice to drink more. In fact, after three weeks these mice began imbibing three times as much alcohol as their more conservative counterparts. This behavioral change, the scientists say, may stem from an abundance of certain alcohol-sensitive proteins in the reward-system region of the brain. The malfunction of the CRH system in the mutant mice, when combined with stress, could provoke an increase in the expression of these proteins, they propose, causing the mice to seek solace in extra drinks.
Spanagel and his colleagues are excited about the possibility that their model will apply to humans. "Patients with alterations in this gene may be particularly susceptible to stress, and may respond with drinking," Spanagel says. If so, by investigating the presence or absence of variants of the gene in their patients, doctors could potentially identify recovering alcoholics who are more likely to experience a stress-induced relapse.
