Abstract
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.
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Acknowledgements
We thank Julien Familiades, Fanny Botreau, Ingrid Waldschmidt, and Claudia Chauvet for help in behavioral procedures (place preference, behavioral sensitization, and intra-venous self-administration); Claire Rampon and Magaly Alonso for help with the immunohistochemistry; Helene Halley for technical assistance and animal care; Jean-Pierre Changeux, Peter Redgrave, Nasser Haddjeri, Manuel Mameli, and Fred Ambroggi for their useful comments on the manuscript.
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Massaly, N., Dahan, L., Baudonnat, M. et al. Involvement of Protein Degradation by the Ubiquitin Proteasome System in Opiate Addictive Behaviors. Neuropsychopharmacol 38, 596–604 (2013). https://doi.org/10.1038/npp.2012.217
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DOI: https://doi.org/10.1038/npp.2012.217
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