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Publication : MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants.

First Author  Deng JV Year  2010
Journal  Nat Neurosci Volume  13
Issue  9 Pages  1128-36
PubMed ID  20711186 Mgi Jnum  J:165279
Mgi Id  MGI:4836785 Doi  10.1038/nn.2614
Citation  Deng JV, et al. (2010) MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci 13(9):1128-36
abstractText  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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