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A key gene for susceptibility to alcoholism discovered

A key gene for susceptibility to alcoholism discovered

A study in mice co-led by Pompeu Fabra University and the Douglas Mental Health University Institute in Canada has revealed that the gene Gpr88 may be a potential target for developing drugs to treat alcoholism.

16.04.2018

Alcohol is the most consumed drug by young people and adults in our society. It acts by complex mechanisms and its chronic consumption produces alterations in the expression of different genes in the areas of the brain responsible for the reward system, emotions and decision-making.

The gene Gpr88 encodes for a receptor linked to G proteins that is precisely expressed predominantly in these areas of the brain. Researchers Rafael Maldonado of Pompeu Fabra University and Brigitte Lina Kieffer of the Douglas Mental Health University Institute have carried out a study that analysed the role of this receptor in alcoholism. The paper has been published in the journal Biological Psychiatry.

For this purpose they used knockout mice for the gene Gpr88 in which this gene was inactivated using genetic engineering to understand its role. They noted that these mice present an increase in the voluntary consumption of and quest for alcohol, both when moderate and high alcohol concentrations were used. To confirm that this behaviour only occurs with alcohol, they checked that these animals had no changes in relation to the search for and consumption of palatable food. 

Rafael Maldonado, head of the Neuropharmacology Laboratory at UPF comments that “alcohol consumption produces a pleasurable sensation partly mediated by increased dopamine release in the nucleus accumbens. However, knockout mice for the gene Gpr88 have a lower capacity of alcohol to increase dopamine in the reward circuit”. For this reason the mutated mice would have to consume more alcohol to achieve similar reward effects to those of the control animals.

They also analysed the patterns of activity in different regions of the brain of resting-state mice using functional magnetic resonance imaging (Rs-fMRI). These knockout mice displayed significant alterations in the mesocorticolimbic system, specifically patterns very similar to those seen in people who have a high risk of suffering alcoholism.

“The Gpr88 gene could be a treatment target of great interest to develop new drugs for the treatment of alcohol addiction. The treatments currently available have limited effectiveness and we need new treatment strategies that allow more effective control of this disease”, concludes Maldonado, full professor of Pharmacology at UPF.

Reference article:

Sami Ben Hamida, Sueli Mendonça-Netto, Tanzil Mahmud Arefin, Md. Taufiq Nasseef, Laura-Joy Boulos, Michael McNicholas, Aliza Toby Ehrlich, Eleanor Clarke, Luc Moquin, Alain Gratton, Emmanuel Darcq, Laura Adela Harsan, Rafael Maldonado, and Brigitte Lina Kieffer. Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional Mesocorticolimbic Networks. Biological Psychiatry, April 2018. https://doi.org/10.1016/j.biopsych.2018.01.026

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