title: Role of Wnt/β-catenin pathway in the nucleus accumbens in long-term cocaine-induced neuroplasticity: a possible novel target for addiction treatment.
abstract: Cocaine addiction is a chronic relapsing disorder characterized by the loss of control over drug-seeking and taking, and continued drug use regardless of adverse consequences. Despite years of research, effective treatments for psycho-stimulant addiction have not been identified. Persistent vulnerability to relapse arises from a number of long-lasting adaptations in the reward circuitry that mediate the enduring response to the drug. Recently, we reported that the activity of the canonical or Wnt/β-catenin pathway in the prefrontal cortex (PFC) is very important in the early stages of cocaine-induced neuroadaptations. In the present work, our main goal was to elucidate the relevance of this pathway in cocaine-induced long-term neuroadaptations that may underlie relapse. We found that a cocaine challenge, after a period of abstinence, induced an increase in the activity of the pathway which is revealed as an increase in the total and nuclear levels of β-catenin (final effector of the pathway) in the nucleus accumbens (NAcc), together with a decrease in the activity of glycogen synthase kinase 3β (GSK3β). Moreover, we found that the pharmacological modulation of the activity of the pathway has long-term effects on the cocaine-induced neuroplasticity at behavioral and molecular levels. All the results imply that changes in the Wnt/β-catenin pathway effectors are long-term neuroadaptations necessary for the behavioral response to cocaine. Even though more research is needed, the present results introduce the Wnt canonical pathway as a possible target to manage cocaine long-term neuroadaptations.
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.|Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Cuesta
authors.affiliation: Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Batuecas
authors.affiliation: Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Severin
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.|Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Alejandrina
authors.initials: A
authors.lastname: Funes
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.|Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Silvana B
authors.initials: SB
authors.lastname: Rosso
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.|Área Toxicología, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Alejandra M
authors.identifier: 0000-0002-1665-6157
authors.initials: AM
authors.lastname: Pacchioni
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D016503:Drug Delivery Systems; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D051176:beta Catenin; D003042:Cocaine
keywords: Wnt canonical pathway; cocaine; lithium chloride; long-term neuroadaptations; nucleus accumbens