Article abstract
Nature Neuroscience 11, 344 - 353 (2008)
Published online: 17 February 2008 | Corrected online: 1 April 2008 | doi:10.1038/nn2054
There is a Corrigendum (May 2008) associated with this Article.
CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking
Sharon M Anderson1,5, Katie R Famous1,5, Ghazaleh Sadri-Vakili3,5, Vidhya Kumaresan1,5, Heath D Schmidt1, Caroline E Bass4, Ernest F Terwilliger4, Jang-Ho J Cha3 & R Christopher Pierce1,2
Abstract
Increases in dopamine and glutamate transmission in the nucleus accumbens independently promote the reinstatement of cocaine seeking, an animal model of relapse. Here we have tested whether cocaine reinstatement in rats depends on interactions between accumbal dopamine and glutamate systems that are mediated by Ca2+/calmodulin-mediated kinase II (CaMKII). We show that stimulation of D1-like dopamine receptors in the nucleus accumbens shell reinstates cocaine seeking by activating L-type Ca2+ channels and CaMKII. Cocaine reinstatement is associated with D1-like dopamine receptor–dependent increases in accumbens shell CaMKII phosphorylated on Thr286 and glutamate receptor 1 (GluR1) phosphorylated on Ser831 (a known CaMKII phosphorylation site), in addition to increases in cell-surface expression of GluR1-containing AMPA receptors in the shell. Consistent with these findings, cocaine reinstatement is attenuated by intra-shell administration of AAV10-GluR1-C99, a vector that impairs the transport of GluR1-containing AMPA receptors. Thus, CaMKII may be an essential link between accumbens shell dopamine and glutamate systems involved in the neuronal plasticity underlying cocaine craving and relapse.
- Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L603, Boston, Massachusetts 02118, USA.
- Department of Psychiatry, Boston University School of Medicine, 715 Albany Street, L603, Boston, Massachusetts 02118, USA.
- MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, Massachusetts 02129, USA.
- Division of Experimental Medicine, Harvard Institutes of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
- These authors contributed equally to this work.
Correspondence to: R Christopher Pierce1,2 e-mail: rcpierce@bu.edu
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