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Transient viral‐mediated overexpression of α‐calcium/calmodulin‐dependent protein kinase II in the nucleus accumbens shell leads to long‐lasting functional upregulation of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptors: dopamine type‐1 receptor and protein kinase A dependence
Author(s) -
Singer B. F.,
Loweth J. A.,
Neve R. L.,
Vezina P.
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07155.x
Subject(s) - ampa receptor , nucleus accumbens , chemistry , downregulation and upregulation , endocrinology , medicine , protein kinase a , antagonist , receptor , nmda receptor , pharmacology , kinase , biology , biochemistry , gene
Calcium/calmodulin‐dependent protein kinase II (CaMKII) activity is necessary for the long‐lasting expression of locomotor sensitization and enhanced drug‐taking observed in rats previously exposed to psychostimulants. Exposure to these drugs also transiently increases αCaMKII levels in the nucleus accumbens (NAcc), an effect that, when mimicked by transient viral‐mediated overexpression of αCaMKII in NAcc shell neurons, leads to long‐lasting enhancement in locomotor responding to amphetamine and NAcc α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA). The present experiments characterized the dopamine (DA) dependence of the functional AMPA receptor upregulation observed long after transient overexpression of αCaMKII. Rats infected with herpes simplex virus‐αCaMKII in the NAcc shell showed a transient increase in αCaMKII levels that peaked at 4 days post‐infection and returned to baseline 8 days later. When challenged with AMPA (0.8 nmol/side) in the NAcc shell at 20 days post‐infection, these rats showed enhanced locomotion compared with controls. This sensitized locomotor response was blocked when AMPA was coinfused with either the DA type‐1 receptor antagonist SCH23390 (0.8 nmol/side) or the protein kinase A inhibitor Rp‐cAMPS (80 nmol/side). Neither SCH23390 nor Rp‐cAMPS produced locomotor effects when infused by itself into the NAcc shell. Furthermore, these antagonists did not block the acute non‐sensitized locomotor response to AMPA observed in control rats. These findings show that transient viral‐mediated overexpression of αCaMKII in neurons of the NAcc shell leads to long‐lasting functional upregulation of AMPA receptors that is DA type‐1 receptor and protein kinase A dependent. Thus, transient increases in levels of αCaMKII in the NAcc shell produce long‐lasting changes in the way that DA and glutamate interact in this site to generate locomotor behavior.