CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking.
Nat Neurosci
; 11(3): 344-53, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18278040
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 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.
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Base de dados:
MEDLINE
Assunto principal:
Dopamina
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Transmissão Sináptica
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Ácido Glutâmico
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Transtornos Relacionados ao Uso de Cocaína
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
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Núcleo Accumbens
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article