Autophosphorylation of alpha isoform of calcium/calmodulin-dependent kinase II regulates alcohol addiction-related behaviors

Autor: Zofia Mijakowska, Kasia Radwanska, Żaneta Matuszek, Kacper Łukasiewicz, Magda Ziółkowska, Anna Trąbczyńska, Szymon Łęski, Michal Lipinski
Rok vydání: 2015
Předmět:
Zdroj: Addiction Biology. 22:331-341
ISSN: 1355-6215
DOI: 10.1111/adb.12327
Popis: The development of addiction is associated with a dysregulation of glutamatergic transmission in the brain reward circuit. α isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is one of the key proteins that regulates structural and functional plasticity of glutamatergic synapses. αCaMKII activity can be controlled by the autophosphorylation of threonine 286. The role of this autophosphorylation in the regulation of addiction-related behaviors has been proposed but is still poorly understood. Here, using αCaMKII autophosphorylation-deficient mutant mice (T286A), we show that, in comparison with wild-type animals, they are less resistant to high doses of alcohol and do not show psychostimulant response neither to alcohol injections nor during voluntary alcohol drinking. T286A mutants are also less prone to develop alcohol addiction-related behaviors including an increased motivation for alcohol, persistent alcohol seeking during withdrawal and alcohol consumption on relapse. Finally, we demonstrate that αCaMKII autophosphorylation regulates also alcohol-induced remodeling of glutamatergic synapses in the hippocampus and amygdala. In conclusion, our data suggest that αCaMKII autophosphorylation-dependent remodeling of glutamatergic synapses is a plausible mechanism for the regulation of the alcohol addiction-related behaviors.
Databáze: OpenAIRE
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