News from the DCEXS-UPF
Alcohol chronic consumption is known to produce alterations in the expression of different genes in the areas of the brain responsible for the reward system, emotions and decision-making. A new study has analysed the role of Gpr88, a gene that encodes for a receptor that is predominantly expressed in these areas of the brain.
In Gpr88 knockout mice, in which this gene was inactivated using genetic engineering, the authors noted an increase in the voluntary consumption of and quest for alcohol. This behaviour was specific for alcohol, since their search for and consumption of palatable food was unaffected.
Rafael Maldonado, head of the Neuropharmacology Laboratory at UPF and one of the authors, comments that “alcohol consumption produces a pleasurable sensation partly mediated by increased dopamine release in the nucleus accumbens. However, in mice lacking Gpr88, alcohol has a lower capacity 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.
The researchers also analysed the patterns of brain activity in 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 results pinpoint the Gpr88 gene as a target of great interest to develop new drugs for the treatment of alcohol addiction.
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