MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants
Open accessAbstract
MeCP2 is a methyl DNA-binding transcriptional regulator that contributes to the development and function of CNS synapses; however, the requirement for MeCP2 in stimulus-regulated behavioral plasticity is not fully understood. Here we show that acute viral manipulation of MeCP2 expression in the nucleus accumbens (NAc) bidirectionally modulates amphetamine (AMPH)-induced conditioned place preference. Mecp2 hypomorphic mutant mice have more NAc GABAergic synapses and show deficient AMPH-induced structural plasticity of NAc dendritic spines. Furthermore, these mice show deficient plasticity of striatal immediate early gene inducibility after repeated AMPH administration. Notably, psychostimulants induce phosphorylation of MeCP2 at Ser421, a site that regulates MeCP2's function as a repressor. Phosphorylation is selectively induced in GABAergic interneurons of the NAc, and its extent strongly predicts the degree of behavioral sensitization. These data reveal new roles for MeCP2 both in mesolimbocortical circuit development and in the regulation of psychostimulant-induced behaviors.
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Neuronal activity induces phosphorylation of MECP2 at Ser421 broadly across the genome.
“Neuronal activity induces the phosphorylation of MECP2 at Ser421 (refs 81–83) broadly across the genome”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [83]
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- Authors
- Deng, J. V., Rodriguiz, R. M., Hutchinson, A. N., Kim, I.-H., Wetsel, W. C., & West, A. E.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- Corresponding author
- West, Anne E
- Venue
- Nature Neuroscience
- Published
- 2010-08-15
- Volume
- 13
- Issue
- 9
- Pages
- 1128-1136
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2928851
- OpenAlex
- W2167717539
- Cited by
- 206
- References
- 49
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 7 · 2022: 14 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 15 · 2015: 21 · 2014: 22 · 2013: 22 · 2012: 22
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (F32DA025447, R01DA022202)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- MeCP2, nucleus accumbens, amphetamine, psychostimulants, transcriptional regulation, GABAergic interneurons, dendritic spine plasticity, conditioned place preference, behavioral sensitization, synaptic development
- MeSH terms
- Amphetamine, Central Nervous System Stimulants, Animals, Conditioning, Classical, Corpus Striatum, Drinking Behavior, gamma-Aminobutyric Acid, Interneurons, Male, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Neuronal Plasticity, Nucleus Accumbens, Phosphorylation, Synapses, Genes, Immediate-Early, Dendritic Spines, Mice, Methyl-CpG-Binding Protein 2
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