期刊
NATURE NEUROSCIENCE
卷 13, 期 9, 页码 1120-U121出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2615
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资金
- US National Institute on Drug Abuse [DA025983]
- Ruth L. Kirschstein National Research Service
- National Alliance for Research on Schizophrenia and Depression (NARSAD)
The X-linked transcriptional repressor methyl CpG binding protein 2 (MeCP2), known for its role in the neurodevelopmental disorder Rett syndrome, is emerging as an important regulator of neuroplasticity in postmitotic neurons. Cocaine addiction is commonly viewed as a disorder of neuroplasticity, but the potential involvement of MeCP2 has not been explored. Here we identify a key role for MeCP2 in the dorsal striatum in the escalating cocaine intake seen in rats with extended access to the drug, a process that mimics the increasingly uncontrolled cocaine use seen in addicted humans. MeCP2 regulates cocaine intake through homeostatic interactions with microRNA-212 (miR-212) to control the effects of cocaine on striatal brain-derived neurotrophic factor (BDNF) levels. These data suggest that homeostatic interactions between MeCP2 and miR-212 in dorsal striatum may be important in regulating vulnerability to cocaine addiction.
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