Sodium butyrate modulates a methamphetamine‐induced conditioned place preference
Accumulating evidence demonstrates that persistent alterations in gene expression accompanying drug abuse were modulated, at least partially, by chromatin modification (Kumar et al., 2005; Maze and Nestler, 2011; Cadet et al., 2013; Rogge and Wood, 2013), among which histone acetylation was the most often studied factor in addictive animal models (Nestler, 2014). It was hypothesized that histone acetylation and subsequent modification in chromatin structure induced longstanding gene expression alterations in the brain and thus contributed to interpret the persistence of addictive behaviors (Renthal et al., 2007; Sanchis‐Segura et al., 2009). With different treatment regimens, previous studies revealed complex alterations of histone acetylation in addictive models of cocaine (Kumar et al., 2005; Renthal et al., 2007), amphetamine (Kalda et al., 2007; Renthal et al., 2008; Shen et al., 2008), and methamphetamine (METH; Shibasaki et al., 2011; Cadet et al., 2013). Moreover, both genetic and pharmacological studies showed that histone deacetylases (HDACs) played an important role in modulating cocaine‐induced conditioned place preference (CPP; Renthal et al., 2007) as well as amphetamine and METH‐induced hyperlocomotor activity (Kim et al., 2008; Arent et al., 2011; Moretti et al., 2011) and behavioral sensitization (Coccurello et al., 2007; Kalda et al., 2007; Shen et al., 2008; Harkness et al., 2013). However, the effects of histone acetylation on distinct phases of METH‐induced CPP remain unclear.
Sodium butyrate (NaB) is a nonselective HDACs inhibitor, which inhibits class I/II HDACs (Harrison and Dexter, 2013) and thus increases histone acetylation and modulates gene expression in the brain (Shen et al., 2008). All of these findings suggest a role for NaB in modulating drug addiction, yet the effects of NaB on distinct phases of METH‐induced CPP remain unclear. Therefore, the current study used a five‐phase CPP procedure to examine the effects of NaB on the acquisition, extinction, and reinstatement of METH‐induced CPP in mice . Our results suggest that NaB plays specific roles in modulating distinct phases of METH‐induced CPP and has considerable therapeutic potential for METH addiction, providing additional evidence for the epigenetic therapeutic perspectives for drug addiction.