Dopaminergic and metabolic features of compulsive alcohol-related behaviors
Sebastien Carnicella
Grenoble Institut Neurosciences – GIN
Team leader « Physiopathologie de la Motivation »

Résumé
Neurobiological mechanisms underlying compulsive alcohol use, a cardinal problem of addiction linked to persistent of this harmful behavior despite its negative consequences, remain elusive. Dopamine (DA), key modulator of motivational processes, is suspected to play an important role in this pathology, but its exact implication remains to be determined. Here, we found that rats expressing a compulsive alcohol-related behavior presented a decrease of DA levels restricted to the dorsolateral-striatum, a main output structure of the DA nigrostriatal pathway. We next chemogenetically mimicked this hypodopaminergia state of the nigrostriatal pathway which led to motivational impairments reminiscent of alcohol withdrawal and to the emergence of compulsive-alcohol related behavior in rats that do not initially express this phenotype, emphasizing a major implication of tonic hypodopaminergic state in alcohol addiction. By taking advantage of the strong inter-individual differences related to compulsive alcohol use we observed, we were also able with NMR-based metabolomics to capture from the serum a specific metabolic profile predicting vulnerability to the development of compulsive alcohol-related behavior. Taking together, these results provide new insights to understand some of the neurobiological mechanisms underlying compulsive alcohol use and open new avenues of research for the development of adapted treatments and biomarkers for individuals at risk to develop compulsive-like ethanol use.

Invité par Olivier Manzoni
Lundi 15 mai 2023 – 11h dans la salle de conférence de l’Inmed