title: AMPAR-independent effect of striatal αCaMKII promotes the sensitization of cocaine reward.
abstract: Changes in CaMKII-regulated synaptic excitability are a means through which experience may modify neuronal function and shape behavior. While behavior in rodent addiction models is linked with CaMKII activity in the nucleus accumbens (NAc) shell, the key cellular adaptations that forge this link are unclear. Using a mouse strain with striatal-specific expression of autonomously active CaMKII (T286D), we demonstrate that while persistent CaMKII activity induces behaviors comparable to those in mice repeatedly exposed to psychostimulants, it is insufficient to increase AMPAR-mediated synaptic strength in NAc shell. However, autonomous CaMKII upregulates A-type K(+) current (IA) and decreases firing in shell neurons. Importantly, inactivating the transgene with doxycycline eliminates both the IA-mediated firing decrease and the elevated behavioral response to cocaine. This study identifies CaMKII regulation of IA in NAc shell neurons as a novel cellular contributor to the sensitization of cocaine reward.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Saïd
authors.initials: S
authors.lastname: Kourrich
authors.forename: Jason R
authors.initials: JR
authors.lastname: Klug
authors.forename: Mark
authors.initials: M
authors.lastname: Mayford
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009924:Organ Culture Techniques; D018091:Receptors, AMPA / Q000502:physiology*; D012201:Reward; D013569:Synapses / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D018091:Receptors, AMPA; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003042:Cocaine