With 1/8 deaths due to a substance of abuse worldwide, addiction is a public health priority, but its pathophysiology remains poorly understood. Genetic modifications of nAChR α5 subunit alter nicotine and cocaine self-administration in rodents (Besson, Forget et Maskos – NISC), and variants in this gene have repeatedly been associated with nicotine, cocaine and alcohol addiction in Humans. We aimed to extend these findings with a series of genotype/phenotype association studies in 491 Caucasian outpatients with severe addictions, considering the nicotinic pathway from a genome-wide DNA microarray. We focused on phenotypes corresponding to rodent self-administration stages. Early relapse of cocaine addiction was associated to a variant in the chaperone protein gene RIC-3 and the polymorphism rs16969968 to more cigarettes smoked/day (both corrected p < 0.05). We will extend this collaboration through a translational research program submitted to the ANR.
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