Implication of hypodopaminergic state of the nigrostriatal pathway in compulsive alcohol-related behaviors
Neurobiological mechanisms underlying compulsive alcohol use, a cardinal problem of addiction, 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. Using chemogenetic, we induced a selective hypodopaminergia of nigrostriatal pathway. This alteration 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. These results identify and demonstrate a major implication of tonic hypodopaminergic state in alcohol addiction and provide new insights to understand neurobiological mechanism underlying compulsive alcohol use.
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