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

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 a...

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Bibliographic Details
Published in:Addiction biology 2017-03, Vol.22 (2), p.331-341
Main Authors: Mijakowska, Zofia, Łukasiewicz, Kacper, Ziółkowska, Magda, Lipiński, Michał, Trąbczyńska, Anna, Matuszek, Żaneta, Łęski, Szymon, Radwanska, Kasia
Format: Article
Language:English
Subjects:
Addictions
Alcohol
alcohol addiction
Alcohol use
Alcoholism
Alcoholism - genetics
Amygdala
Amygdala - metabolism
Animals
Behavior, Animal
Calcium
Calcium-binding protein
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics
Calmodulin
Central Nervous System Depressants - pharmacology
Deficient mutant
Drinking behavior
Drug addiction
Drug-Seeking Behavior
Ethanol - pharmacology
Female
Functional plasticity
Glutamatergic transmission
Glutamic Acid - metabolism
Hippocampus - metabolism
IntelliCages
Male
Mice
Motivation
Mutation
Phosphorylation - genetics
PSD‐95
Reinforcement
Structure-function relationships
Synapses - metabolism
Threonine
Withdrawal
αCaMKII
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Summary: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. 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 regulate glutamatergic synapses. Using α CaMKII autophosphorylation‐deficient mutant mice, we show that αCaMKII autophosphorylation is involved in development of alcohol addiction‐related behaviors including an increased motivation for alcohol, persistent alcohol seeking during withdrawal, and alcohol consumption on relapse.
ISSN:1355-6215
1369-1600
DOI:10.1111/adb.12327