?CaMKII controls the establishment of cocaine's reinforcing effects in mice and humans

Easton AC, Lourdusamy A, Havranek M, Mizuno K, Solati J, Golub Y, Clarke TK, Vallada H, Laranjeira R, Desrivieres S, Moll G, Moessner R, Kornhuber J, Schumann G, Giese KP, Fernandes C, Quednow BB, Mueller CP (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Translational Psychiatry Springer Nature

Book Volume: 4

Pages Range: e457

DOI: 10.1038/tp.2014.97

Abstract

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (?CaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of ?CaMKII was shown to accelerate learning. Thus, we investigated the role of ?CaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that ?CaMKII autophosphorylation-deficient ?CaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that ?CaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in ?CaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that ?CaMKII controls the speed for the establishment of cocaine's reinforcing effects.

Authors with CRIS profile

Jalal Solati Department of Child and Adolescent Mental Health Yulia Golub Department of Child and Adolescent Mental Health Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

King’s College London GB United Kingdom (GB) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) University of Pennsylvania US United States (USA) (US) University of São Paulo / Universidade de São Paulo (USP) BR Brazil (BR) Federal University of São Paulo / Universidade Federal de São Paulo (UNIFESP) BR Brazil (BR) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Easton, A.C., Lourdusamy, A., Havranek, M., Mizuno, K., Solati, J., Golub, Y.,... Mueller, C.P. (2014). ?CaMKII controls the establishment of cocaine's reinforcing effects in mice and humans. Translational Psychiatry, 4, e457. https://doi.org/10.1038/tp.2014.97

MLA:

Easton, A. C., et al. "?CaMKII controls the establishment of cocaine's reinforcing effects in mice and humans." Translational Psychiatry 4 (2014): e457.

BibTeX: Download