Erkrankungen des Nervensystems -

For further information, please read the article "Alcohol Addiction: Stressed-Out Mice Hit the Bottle"

Day-Night Rhythm Disturbances Influence Alcohol Consumption

People whose internal clock is out of phase would appear to have a greater attraction to alcohol, according to the research findings of the German National Genome Research Network (NGFN). A group of scientists led by Professor Rainer Spanagel at the Central Institute of Mental Health, University of Heidelberg, have observed that mice with a specific mutation in the per2 gene demonstrate a particular affinity to alcohol.

The per2 gene acts in combination with other hereditary factors on the mechanisms that control the sleep cycle. This cycle is disturbed in mice with a mutated per2 gene.

Professor Spanagel, who is leading the project, explains that these findings are probably transferable to humans: “We already know that adolescents with specific mutations in the per2 gene are heavier drinkers than other youngsters of the same age. It is also proven that shift-workers, airline staff and other people with a disturbed circadian rhythm are more likely to suffer from problems related to alcohol.”

Mice with this mutation in the per2 gene drank three times as much alcohol as healthy controls when given the choice between alcohol and water. When the scientists performed closer examinations of these animals, they discovered a possible explanation for this behavior: The brain of the genetically modified mice contained high concentrations of the neurotransmitter glutamate.

Glutamate can also be found in high concentrations in the brain tissue of alcoholic human patients. In the past, this was attributed to the fact that the body tries to compensate for the soporific effect of alcohol by producing greater quantities of glutamate, which is a stimulant. But the latest research findings provide evidence that certain people, just like the mice with a mutated per2 gene, have relatively high levels of glutamate in their brain tissue from the outset. As a result, they have a greater tolerance to alcohol and therefore consume larger quantities.

It is possible to weaken the effect of glutamate on the brain by treating patients with Acamprosat. It is for this reason that this drug is frequently used in the treatment of alcoholism, but not all patients respond to the therapy.

The research team in Heidelberg achieved very good results when treating their alcoholic mice with this drug: It lowered the concentration of glutamate in the animals’ brains – and at the same time moderated their consumption of alcohol. These experiments provide useful information that could be transferred to the treatment of alcoholism in human patients.

Spanagel: “Our hypothesis is that the drug is mainly effective on patients whose glutamate metabolism is already disturbed, for instance as the result of a mutation in the per2 gene. We are now working on a test to reliably identify these patients, in the hope of soon being able to predict which patients can be effectively treated with Acamprosat.”

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