Role of Wnt/[beta]-catenin pathway in the nucleus accumbens in long-term cocaine-induced neuroplasticity: a possible novel target for addiction treatment

• Published in: Journal of neurochemistry Vol. 140; no. 1; p. 114
• Main Authors: Cuesta, Santiago, Batuecas, Jorgelina, Severin, Maria J, Funes, Alejandrina, Rosso, Silvana B, Pacchioni, Alejandra M
• Format: Journal Article
• Language: English
• Published: New York Blackwell Publishing Ltd 01-01-2017
• Subjects: Addictions; Cocaine; Neurochemistry; Rodents; Substance abuse treatment
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.13863

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/[beta]-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 [beta]-catenin (final effector of the pathway) in the nucleus accumbens (NAcc), together with a decrease in the activity of glycogen synthase kinase 3[beta] (GSK3[beta]). 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/[beta]-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.