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Chris Peirce"CaM-KII: a biochemical bridge linking nucleus accumbens dopamine and glutamate systems in the reinstatement of cocaine seeking"

Abstract :


Increases in dopamine and glutamate transmission in the nucleus accumbens independently promote the reinstatement of cocaine seeking, an animal model of relapse?
Our data demonstrate that cocaine reinstatement depends on interactions between accumbal dopamine and glutamate systems that are mediated by CaMKII.? Stimulation of D1-like dopamine receptors in the accumbens shell reinstated cocaine seeking via activation of L-type calcium channels.? Reinstatement of cocaine seeking also was attenuated by intra-accumbal shell administration of a CaMKII inhibitor.? Cocaine reinstatement was associated with dopamine receptor-dependent increases in accumbens shell CaMKII-pThr286 and GluR1-pSer831, a CaMKII phosphorylation site on this AMPA glutamate receptor subunit.? Finally, cocaine reinstatement was attenuated by intra-shell administration of AAV-GluR1-C99, which expresses a peptide that impairs the trafficking of GluR1-containing AMPA receptors.? Collectively, these results indicate that CaMKII is the critical link between accumbens shell dopamine and glutamate systems involved in the neuronal plasticity underlying cocaine craving and relapse.

Selected publications

Anderson SM, Famous KR, Sadri-Vakili G, Kumaresan V, Schmidt HD, Bass CE, Terwilliger EF, Cha JH, Pierce RC.
CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking.
Nat Neurosci. 2008 Mar;11(3):344-53. Epub 2008 Feb 17.
Famous KR, Schmidt HD, Pierce RC.
When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat.
Neurosci Lett. 2007 Jun 13;420(2):169-73. Epub 2007 May 3.

Anderson SM, Schmidt HD, Pierce RC.
Administration of the D2 dopamine receptor antagonist sulpiride into the shell, but not the core, of the nucleus accumbens attenuates cocaine priming-induced reinstatement of drug seeking.
Neuropsychopharmacology. 2006 Jul;31(7):1452-61. Epub 2005 Oct 5.

Serge Ahmed