title: Autophosphorylation of alpha isoform of calcium/calmodulin-dependent kinase II regulates alcohol addiction-related behaviors.
abstract: 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.
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Mijakowska
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Kacper
authors.initials: K
authors.lastname: Łukasiewicz
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Magda
authors.initials: M
authors.lastname: Ziółkowska
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Lipiński
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Trąbczyńska
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Żaneta
authors.initials: Ż
authors.lastname: Matuszek
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Łęski
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Kasia
authors.initials: K
authors.lastname: Radwanska
mesh_terms: D000437:Alcoholism / Q000235:genetics; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D058999:Drug-Seeking Behavior; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D009042:Motivation; D009154:Mutation; D010766:Phosphorylation / Q000235:genetics; D013569:Synapses / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse
keywords: IntelliCages; PSD-95; alcohol addiction; αCaMKII