Long-lasting behavioral syndromes associated with chronic cocaine exposure may result from dysregulation of the global transcriptional machinery. Maze et al. observed that histone lysine methylation in the nucleus accumbens plays a critical role in mediating the regulation of gene expression in response to repeated cocaine self-administration. Chronic cocaine was linked to overall reductions in dimethylation of lysine 9 of histone 3 (H3K9) in this brain region. Repressing H3K9 after chronic cocaine administration facilitated reward-related changes in behavior. The authors identified the methyltransferase G9a as an essential mediator and an important regulator of dendritic spine plasticity. Down-regulation of G9a was linked to the transcription factor ΔFosB.
I. Maze, H. E. Covington III, D. M. Dietz, Q. LaPlant, W. Renthal, S. J. Russo, M. Mechanic, E. Mouzon, R. L. Neve, S. J. Haggarty, Y. Ren, S. C. Sampath, Y. L. Hurd, P. Greengard, A. Tarakhovsky, A. Schaefer, E. J. Nestler, Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science 327, 213–216 (2010). [Abstract] [Full Text]