Send to

Choose Destination
Nat Neurosci. 2008 Mar;11(3):344-53. doi: 10.1038/nn2054. Epub 2008 Feb 17.

CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking.

Author information

Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L603, Boston, Massachusetts 02118, USA.

Erratum in

  • Nat Neurosci. 2008 May;11(5):617.


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 Ca(2+)/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 Ca(2+) 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.

[Indexed for MEDLINE]

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center