Chunk #25 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1E. Other Drugs of Abuse and Histone Acetylation and Deacetylation Mechanisms
cocaine sensitivity (Malvaez, Mhillaj, Matheos, Palmery, & Wood, 2011). Acute cocaine was shown to rapidly induce H4 acetylation, but not H3, at the cFos promoter, whereas chronic cocaine administration induced histone H3 acetylation at the BDNF promoter (Kumar et al., 2005). HDAC inhibition through pharmacological approaches using sodium butyrate and TSA and using genetic approaches (HDAC5 knockout), was able to potentiate cocaine’s behavioral effects whereas overexpression of HDAC4 and HDAC5 were able to decrease the behavioral responses to cocaine (Kumar et al., 2005; Renthal et al., 2007). Others have also shown HDAC isoform specific regulation of cocaine behaviors (Host, Dietrich, Carouge, Aunis, & Zwiller, 2011; Malvaez et al., 2013; Schroeder et al., 2008). In the case of the sirtuin class of HDACs, chronic cocaine exposure was shown to induce SIRT1 and SIRT2 and regulate cocaine self-administration and reward. This was shown to occur due to increased H3 acetylation and delta-fosB binding to the SIRT promoters (Renthal et al., 2009). Regulation of HDAC activity has also been implicated in enhancement of morphine-induced locomotor sensitization and conditioned place preference (Sanchis-Segura, Lopez-Atalaya, & Barco, 2009) and in nicotine preference (Pastor, Host, Zwiller, & Bernabeu, 2011). All these studies emphasize the complexity of HDAC
