AMPAR-independent effect of striatal αCaMKII promotes the sensitization of cocaine reward.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Saïd KourrichMark J Thomas

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.

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Citations

Mar 6, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Alanna C EastonMarcella Rietschel
Jan 25, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jessica A LowethPaul Vezina
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Jun 13, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jakub JedynakMark J Thomas
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Oct 25, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaojie LiuQing-song Liu
Nov 19, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A J RobisonEric J Nestler
Jun 4, 2020·Psychopharmacology·Katherine R Tonn EisingerPaul G Mermelstein
Dec 18, 2015·Trends in Pharmacological Sciences·Christian P MüllerK Peter Giese

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