Neuronal pentraxins modulate cocaine-induced neuroadaptations

Alejandra M. Pacchioni, Joseph Vallone, Paul F Worley, Peter W. Kalivas

Research output: Contribution to journalArticle

Abstract

Neuronal pentraxins (NPs) function in the extracellular matrix to bind α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Three NPs have been described, neuronal activity-regulated pentraxin (Narp), which is regulated as an immediate early gene, NP1, and neuronal pentraxin receptor (NPR). Narp and NP1 enhance synaptogenesis and glutamate signaling by clustering AMPA receptors, whereas NPR contributes to removing AMPA receptors during group I metabotropic glutamate receptor-dependent long-term depression. Here, we examine mice with genetic deletions [knockout (KO)] of each NP to assess their contributions to cocaine-induced neuroplasticity. Consistent with a shared AMPA receptor clustering function for Narp and NP1, deletion of either NP caused similar behavioral alterations. Thus, although both Narp and NP1 deletion promoted cocaine-induced place preference, NPR deletion was without effect. In addition, although Narp and NP1 KO showed reduced time in the center of a novel environment, NPR KO mice spent more time in the center. Finally, although Narp and NP1 KO mice showed blunted locomotion after AMPA microinjection into the accumbens 3 weeks after discontinuing repeated cocaine injections, the AMPA response was augmented in NPR KO. Likewise, endogenous glutamate release elicited less motor activity in Narp KO mice. Consistent with reduced AMPA responsiveness after chronic cocaine in Narp KO mice, glutamate receptor 1 was reduced in the PSD fraction of Narp KO mice withdrawn from cocaine. These data indicate that NPs differentially contribute to cocaine-induced plasticity in a manner that parallels their actions in synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)183-192
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume328
Issue number1
DOIs
Publication statusPublished - Jan 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Medicine(all)

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