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

Autor:	Ceglia I; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065., Lee KW; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065., Cahill ME; Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Graves SM; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Dietz D; Department of Pharmacology and Toxicology, Research Institute on Addictions, Program in Neuroscience, State University of New York at Buffalo, Buffalo, NY 14214., Surmeier DJ; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Nestler EJ; Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Nairn AC; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508., Greengard P; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; kimyo@rockefeller.edu greengard@rockefeller.edu., Kim Y; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; kimyo@rockefeller.edu greengard@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Feb 07; Vol. 114 (6), pp. 1395-1400. Date of Electronic Publication: 2017 Jan 23.
DOI:	10.1073/pnas.1621185114
Abstrakt:	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. Here we report that mice in which WAVE1 was 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 activity-mediated feedback regulation of glutamatergic synapses. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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