Transient viral-mediated overexpression of -calcium/calmodulin-dependent protein kinase II in the nucleus accumbens shell leads to long-lasting functional upregulation of -amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors: Dopamine type-1 receptor and protein kinase A dependence

B. F. Singer, J. A. Loweth, R. L. Neve, P. Vezina

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 CaMKII levels in the nucleus accumbens (NAcc), an effect that, when mimicked by transient viral-mediated overexpression of CaMKII in NAcc shell neurons, leads to long-lasting enhancement in locomotor responding to amphetamine and NAcc -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 CaMKII. Rats infected with herpes simplex virus-CaMKII in the NAcc shell showed a transient increase in CaMKII 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 CaMKII 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 CaMKII in the NAcc shell produce long-lasting changes in the way that DA and glutamate interact in this site to generate locomotor behavior.

Original languageEnglish (US)
Pages (from-to)1243-1251
Number of pages9
JournalEuropean Journal of Neuroscience
Volume31
Issue number7
DOIs
StatePublished - Apr 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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