Dnmt3a2 in the Nucleus Accumbens Shell Is Required for Reinstatement of Cocaine Seeking

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Nazzareno CannellaRainer Spanagel

Abstract

Epigenetic mechanisms have gained increasing attention as regulators of synaptic plasticity and responsiveness to drugs of abuse. In particular, it has been shown that the activity of the DNA methyltransferase 3a (Dnmt3a) mediates certain long-lasting effects of cocaine. Here we examined the role of the Dnmt isoforms, Dnmt3a1 and Dnmt3a2, within the nucleus accumbens (NAc) on transcriptional activity of immediate early genes (IEGs) and acute and long-lasting responsiveness to cocaine and cocaine conditioned cues. Using primary striatal cultures, we show that transcription of Dnmt3a2, but not that of Dnmt3a1, is activated by dopamine D1 receptor signaling and that knockdown of Dnmt3a2 using viral vector-mediated expression of Dnmt3a2-specific shRNAs impairs induction of the IEGs, Arc, FosB, and Egr2 Acute cocaine administration increases expression of Dnmt3a2 but not that of Dnmt3a1 in the NAc shell. In contrast, in the NAc core, expression of Dnmt3a1 and Dnmt3a2 was unaffected by cocaine administration. shRNA-mediated knockdown of Dnmt3a2 in vivo impairs the induction of IEGs, including Egr2 and FosB indicating that Dnmt3a2 regulates cocaine-dependent expression of plasticity genes in the rat NAc shell. Cocaine self-administrat...Continue Reading

Citations

Sep 15, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Morgan E ZipperlyJeremy J Day
Feb 2, 2020·Nature Communications·Kubra Gulmez KaracaAna M M Oliveira
Oct 14, 2020·Molecular Psychiatry·Kathryn VaillancourtGustavo Turecki
Oct 18, 2020·Biological Psychiatry·Craig T WernerXuan Li
Jun 4, 2021·Molecular Psychiatry·Collin D Teague, Eric J Nestler
Jun 12, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hailei YuChunling Ma

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