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Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity
Open accessAbstract
Repeated exposure to cocaine causes sensitized behavioral responses and increased dendritic spines on medium spiny neurons of the nucleus accumbens (NAc). We find that cocaine regulates myocyte enhancer factor 2 (MEF2) transcription factors to control these two processes in vivo. Cocaine suppresses striatal MEF2 activity in part through a mechanism involving cAMP, the regulator of calmodulin signaling (RCS), and calcineurin. We show that reducing MEF2 activity in the NAc in vivo is required for the cocaine-induced increases in dendritic spine density. Surprisingly, we find that increasing MEF2 activity in the NAc, which blocks the cocaine-induced increase in dendritic spine density, enhances sensitized behavioral responses to cocaine. Together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine and suggest that reducing MEF2 activity (and increasing spine density) in NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine.
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“The transcription factor MEF2 controls a program of gene expression that has a role in developmental synapse elimination26,29,65,66.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [66]
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Metadata
- Authors
- Pulipparacharuvil, S., Renthal, W., Hale, C. F., Taniguchi, M., Xiao, G., Kumar, A., Russo, S. J., Sikder, D., Dewey, C. M., Davis, M. M., Greengard, P., Nairn, A. C., Nestler, E. J., & Cowan, C. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Yale University (US)
- Rockefeller University (US)
- Corresponding author
- Cowan, Christopher W.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 59
- Issue
- 4
- Pages
- 621-633
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2626175
- OpenAlex
- W2047660382
- Cited by
- 281
- References
- 42
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 14 · 2023: 4 · 2022: 16 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 16 · 2016: 11 · 2015: 19 · 2014: 14 · 2013: 25 · 2012: 38
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Whitehall Foundation
- National Institute of Mental Health (P50MH074866)
- National Institute on Drug Abuse (P01DA010044, P01DA008227, R01DA007359)
- 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
- cocaine, MEF2 transcription factors, nucleus accumbens, dendritic spines, synaptic plasticity, behavioral sensitization, cAMP signaling, calmodulin signaling, calcineurin, striatum
- MeSH terms
- Adaptation, Physiological, Cyclic AMP, Animals, Behavior, Animal, Cells, Cultured, Cocaine, Drug Administration Schedule, Male, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Nucleus Accumbens, Synapses, Down-Regulation, Neostriatum, Rats, Sprague-Dawley, Myogenic Regulatory Factors, Dopamine Uptake Inhibitors, Cyclin-Dependent Kinases, Rats, Long-Evans, Gene Expression Profiling, Dendritic Spines, Mice, Rats, MEF2 Transcription Factors
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