MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Deng, JV; Wan, Y; Wang, X; Cohen, S; Wetsel, WC; Greenberg, ME; Kenny, PJ; Calakos, N; West, AE

Published Date

  • March 2014

Published In

Volume / Issue

  • 34 / 13

Start / End Page

  • 4519 - 4527

PubMed ID

  • 24671997

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.2821-13.2014

Language

  • eng