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Publication : MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity.

First Author  Deng JV Year  2014
Journal  J Neurosci Volume  34
Issue  13 Pages  4519-27
PubMed ID  24671997 Mgi Jnum  J:210455
Mgi Id  MGI:5571215 Doi  10.1523/JNEUROSCI.2821-13.2014
Citation  Deng JV, et al. (2014) MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity. J Neurosci 34(13):4519-27
abstractText  The methyl-DNA binding protein MeCP2 is emerging as an important regulator of drug reinforcement processes. Psychostimulants induce phosphorylation of MeCP2 at Ser421; however, the functional significance of this posttranslational modification for addictive-like behaviors was unknown. Here we show that MeCP2 Ser421Ala knock-in mice display both a reduced threshold for the induction of locomotor sensitization by investigator-administered amphetamine and enhanced behavioral sensitivity to the reinforcing properties of self-administered cocaine. These behavioral differences were accompanied in the knock-in mice by changes in medium spiny neuron intrinsic excitability and nucleus accumbens gene expression typically observed in association with repeated exposure to these drugs. These data show that phosphorylation of MeCP2 at Ser421 functions to limit the circuit plasticities in the nucleus accumbens that underlie addictive-like behaviors.
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