Stressed Mutant Mice Hit the Bottle

3 May 2002 (All day)

Stress response. Mutant mice drank more alcohol after traumatic experiences.

Some people can be moderate drinkers for years, only to become mired in alcohol after a stressful life event. A new mouse model described may help explain why. In the genetically altered mice, stress apparently acts as a catalyst that makes them--perhaps permanently--more prone to drink.

The mice in question are lacking a key component of their stress response system, a receptor that picks up on corticotropin-releasing hormone (CRH). Previous studies suggest that these mice have a blunted stress response. They're less anxiety-prone than normal mice, eagerly exploring well-lit boxes that nocturnal rodents normally avoid.

Because stress-induced drinking in humans has been shown to have a genetic component, behavioral pharmacologists Inge Sillaber, Rainer Spanagel, and colleagues at the Max Planck Institute of Psychiatry in Munich, Germany, wanted to see how the loss of the CRH receptor affected the animals' drinking habits. Under normal conditions, both mutant and normal mice are moderate tipplers, drinking some alcohol but choosing pure water most of the time. But after being put through two difficult experiences, the mice diverged. In one, a male mouse was put into the cage of a hostile stranger for a brief period 3 days in a row. In another, the mice had to spend 5 minutes in a container of water, unable to get out, for 3 days in a row.

None of the mice's drinking behavior changed during or immediately after the test, the researchers report. But alcohol consumption by the mutant mice began to rise a couple of weeks after the unfriendly cage visits, and a month afterward, their drinking had more than doubled, whereas that of the normal mice hadn't changed. What's more, the authors report, the mutants were still drinking substantially more than the controls 6 months after their unpleasant involuntary swims, the team reports in the 3 May issue of Science.

Exactly how loss of the CRH receptor alters the animals' drinking habits is not clear. The mutants don't appear to be any more shaken up by the stressful situations than are the normal mice. And because they don't start drinking more right away, they're not relying on alcohol to restore their courage. Jane Stewart of Concordia University in Montreal, Canada, who studies the involvement of CRH receptors in addictive behavior, explains that "the stress may activate pathways that have nothing directly to do with fear and anxiety but which alter the approach to alcohol itself."

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