title: CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in 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. 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.
authors.affiliation: Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L603, Boston, Massachusetts 02118, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Katie R
authors.initials: KR
authors.lastname: Famous
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Sadri-Vakili
authors.forename: Vidhya
authors.initials: V
authors.lastname: Kumaresan
authors.forename: Heath D
authors.initials: HD
authors.lastname: Schmidt
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Bass
authors.forename: Ernest F
authors.initials: EF
authors.lastname: Terwilliger
authors.forename: Jang-Ho J
authors.initials: JH
authors.lastname: Cha
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Pierce
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D004110:Diltiazem / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013912:Threonine / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003042:Cocaine; D004110:Diltiazem; D004298:Dopamine; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D018698:Glutamic Acid; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D013912:Threonine