METABOLIC DEREGULATIONS IN ALCOHOL ADDICTION

Alcohol addiction is a major health and economical concern. Compulsivity, substance seeking despite awareness of its negative effects, is the hallmark of addiction. Preventing the shift from controlled to compulsive alcohol seeking is crucial to treat alcohol addiction and reduce the burden of this disease. However, the biological and molecular mechanisms triggering compulsive alcohol seeking remain mainly unknown, preventing the development of efficient treatments.
In the case of multifactorial and complex diseases such as alcohol addiction, metabolomics appears as a powerful tool. Metabolome being at the end of the cellular cascade, it is closest to the phenotype, therefore, global assessment of the metabolism could enlighten new mechanisms responsible for this particular disease.
A first metabolite seems of interest, glycine. Glycine is an inhibitory neurotransmitter, also involved in glutamatergic and dopaminergic transmissions. Glycine is suspected to act on multiple aspects of alcohol addiction.
Additionally, imbalance between Glutamate and GABA, in the striatum for instance, has been previously implicated with alcohol consumption.
However, implication of these metabolites in compulsive alcohol seeking remains to be investigated.
Using a compulsive alcohol seeking preclinical model, with addition of patch-clamp recordings, we aim to confirm the implication of metabolism, and in particular glycine, glutamate and GABA, in compulsive alcohol seeking and to better understand its influence in glutamate-dopamine signalling in this context. Clarifying these mechanisms hold promise for better diagnosis and the development of efficient curative or preventive therapies for alcohol addiction.