title: Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors.
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.
authors.affiliation: Université de Toulouse, Université Paul Sabatier, Toulouse Cedex 9, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Massaly
authors.forename: Lionel
authors.initials: L
authors.lastname: Dahan
authors.forename: Mathieu
authors.initials: M
authors.lastname: Baudonnat
authors.forename: Caroline
authors.initials: C
authors.lastname: Hovnanian
authors.forename: Khaoula
authors.initials: K
authors.lastname: Rekik
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.forename: Vincent
authors.initials: V
authors.lastname: David
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pech
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Zajac
authors.forename: Pascal
authors.initials: P
authors.lastname: Roullet
authors.forename: Lionel
authors.initials: L
authors.lastname: Mouledous
authors.forename: Bernard
authors.initials: B
authors.lastname: Frances
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism* / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000523:psychology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D009020:Morphine; D046988:Proteasome Endopeptidase Complex