Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors.

Nicolas Massaly, Lionel Dahan, Mathieu Baudonnat, Caroline Hovnanian, Khaoula Rekik, Marcello Solinas, Vincent David, Stéphane Pech, Jean-Marie Zajac, Pascal Roullet, Lionel Mouledous, Bernard Frances
Neuropsychopharmacol. 2012-11-21; 38(4): 596-604
DOI: 10.1038/npp.2012.217

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Plastic changes in the nucleus accumbens (NAcc), a structure occupying a key position in the neural circuitry related to motivation, are among the critical
cellular processes responsible for drug addiction. During the last decade, it has been shown that memory formation and related neuronal plasticity may rely not only on protein synthesis but also on protein degradation by the ubiquitin proteasome system (UPS). In this study, we assess the role of protein degradation
in the NAcc in opiate-related behaviors. For this purpose, we coupled behavioral experiments to intra-accumbens injections of lactacystin, an inhibitor of the
UPS. We show that protein degradation in the NAcc is mandatory for a full range of animal models of opiate addiction including morphine locomotor sensitization, morphine conditioned place preference, intra-ventral tegmental area morphine self-administration and intra-venous heroin self-administration but not for discrimination learning rewarded by highly palatable food. This study provides the first evidence of a specific role of protein degradation by the UPS in addiction.


Auteurs Bordeaux Neurocampus