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. Author manuscript; available in PMC: 2010 May 14.
Published in final edited form as: Neuron. 2009 May 14;62(3):335–348. doi: 10.1016/j.neuron.2009.03.026

Fig. 3. Validation of sirtuins as a novel target for cocaine in the NAc.

Fig. 3

A. Changes in histone H3 and H4 acetylation, H3 K9/K27 methylation, and ΔFosB and phospho-CREB binding at the Sirt1 and Sirt2 gene promoters in the NAc after chronic (7 days) cocaine. A short red bold line along the x-axis indicates the position of an AP1 site. Significant changes are shown as solid lines. B. Quantitative ChIP confirmed cocaine-induced increases in H3 acetylation at the Sirt1 (left) and Sirt2 (right) gene promoters in an independent cohort of mice (p < 0.05, n = 3–6). Cocaine-induced ΔFosB binding was also confirmed for the Sirt2 promoter (p < 0.05, n = 3–6). This chromatin regulation is associated with significant increases in Sirt1 and Sirt2 (p < 0.05, n = 7–8) mRNA levels in the NAc. C. As well, SIRT1 and SIRT2 catalytic activity was significantly increased in NAc after chronic cocaine administration (p < 0.05, n = 7–8).

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