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

Saïd Kourrich, Jason R. Klug, Mark Mayford, Mark J. Thomas

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 up regulates 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.

Original languageEnglish (US)
Pages (from-to)6578-6586
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number19
DOIs
StatePublished - May 9 2012

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Corpus Striatum
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Reward
Cocaine
Nucleus Accumbens
Neurons
Doxycycline
Transgenes
Rodentia
Up-Regulation

ASJC Scopus subject areas

  • Neuroscience(all)

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AMPAR-independent effect of striatal αCaMKII promotes the sensitization of cocaine reward. / Kourrich, Saïd; Klug, Jason R.; Mayford, Mark; Thomas, Mark J.

In: Journal of Neuroscience, Vol. 32, No. 19, 09.05.2012, p. 6578-6586.

Research output: Contribution to journalArticle

Kourrich, Saïd ; Klug, Jason R. ; Mayford, Mark ; Thomas, Mark J. / AMPAR-independent effect of striatal αCaMKII promotes the sensitization of cocaine reward. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 19. pp. 6578-6586.
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