WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

Ilaria Ceglia, Ko Woon Lee, Michael E. Cahill, Steven M. Graves, David Dietz, Dalton J. Surmeier, Eric J. Nestler, Angus C. Nairn, Paul Greengard, Yong Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) complex-mediated actin polymerization. Our previous studies have found WAVE1 to be inhibited by Cdk5-mediated phosphorylation in brain and to play a role in the regulation of dendritic spine morphology. Herewe report thatmice inwhich WAVE1was knocked out (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but not mice where WAVE1 was knocked out in neurons expressing the D2 dopamine receptor (D2-KO), exhibited a significant decrease in place preference associated with cocaine. In contrast to wild-Type (WT) and WAVE1 D2-KO mice, cocaine-induced sensitized locomotor behavior was not maintained in WAVE1 D1-KO mice. After chronic cocaine administration and following withdrawal, an acute cocaine challenge induced WAVE1 activation in striatum, which was assessed by dephosphorylation. The cocaine-induced WAVE1 dephosphorylation was attenuated by coadministration of either a D1 dopamine receptor or NMDA glutamate receptor antagonist. Upon an acute challenge of cocaine following chronic cocaine exposure and withdrawal, we also observed in WT, but not in WAVE1 D1-KO mice, a decrease in dendritic spine density and a decrease in the frequency of excitatory postsynaptic AMPA receptor currents in medium spiny projection neurons expressing the D1 dopamine receptor (D1-MSNs) in the nucleus accumbens. These results suggest that WAVE1 is involved selectively in D1-MSNs in cocaine-evoked neuronal activitymediated feedback regulation of glutamatergic synapses.

Original languageEnglish (US)
Pages (from-to)1395-1400
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number6
DOIs
StatePublished - Feb 7 2017

Keywords

  • Cdk5
  • Cocaine
  • Medium spiny projection neurons
  • Striatum
  • Wave1

ASJC Scopus subject areas

  • General

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