Differential Regulation of MeCP2 Phosphorylation in the CNS by Dopamine and Serotonin
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Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, here we examined the ability of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) to induce pMeCP2. Selective blockade of the DA transporter (DAT) or the 5-HT transporter (SERT), but not the NE transporter (NET), was sufficient to induce pMeCP2 in the CNS. DAT blockade induced pMeCP2 in the prelimbic cortex (PLC) and nucleus accumbens (NAc), whereas SERT blockade induced pMeCP2 only in the NAc. Administration of selective DA and 5-HT receptor agonists was also sufficient to induce pMeCP2; however, the specific combination of DA and 5-HT receptors activated determined the regional- and cell-type specificity of pMeCP2 induction. The D(1)-class DA receptor agonist SKF81297 induced pMeCP2 widely; however, coadministration of the D(2)-class agonist quinpirole restricted the induction of pMeCP2 to GABAergic interneurons of the NAc. Intra-striatal injection of the adenylate cyclase activator forskolin was sufficient to induce pMeCP2 in medium-spiny neurons, suggesting that the combinatorial regulation of cAMP by different classes of DA and 5-HT receptors may contribute to the cell-type specificity of pMeCP2 induction. Consistent with the regulation of pMeCP2 by multiple monoamine neurotransmitters, genetic disruption of any single monoamine transporter in DAT-, SERT-, and NET-knockout mice failed to eliminate AMPH-induced pMeCP2 in the NAc. Together, these studies indicate that combinatorial signaling through DA and 5-HT receptors can regulate the brain region- and cell-type specific pMeCP2 in the CNS.
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It has been suggested that MeCP2 protein normally functions in the NAc to limit the rewarding properties of psychostimulants, and that psychostimulant or DA receptor-induced phosphorylation of MeCP2 may be involved in the rewarding properties of drugs of abuse such as amphetamines.
“It has been suggested that MeCP2 protein normally functions in the NAc to limit the rewarding properties of psychostimulants, and that psychostimulant or DA receptor-induced phosphorylation of MeCP2 may be involved in the rewarding properties of drugs of abuse such as amphetamines [700].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [700]
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- Authors
- Hutchinson, A. N., Deng, J. V., Aryal, D. K., Wetsel, W. C., & West, A. E.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- Corresponding author
- West, Anne E
- Venue
- Neuropsychopharmacology
- Published
- 2011-09-28
- Volume
- 37
- Issue
- 2
- Pages
- 321-337
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3242304
- OpenAlex
- W2131955548
- Cited by
- 31
- References
- 65
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- dopamine, serotonin, norepinephrine, monoamines, amphetamine, dopamine transporter, serotonin transporter, norepinephrine transporter, dopamine D1 receptor, dopamine D2 receptor, quinpirole, SKF 81297, GABAergic interneurons, medium spiny neurons, nucleus accumbens, prelimbic cortex, cAMP signaling, cell type specificity, brain region specificity
- MeSH terms
- Reboxetine, Animals, Brain, Cells, Cultured, Dopamine, Drug Interactions, Colforsin, Gene Expression Regulation, Male, Microinjections, Morpholines, Motor Activity, Phosphorylation, Piperazines, Quipazine, Serotonin, Citalopram, Mice, Knockout, Dopamine Agonists, Plasma Membrane Neurotransmitter Transport Proteins, Mice, Methyl-CpG-Binding Protein 2, Molecular Imaging, GABAergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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