On the other hand, miR-1 has been reported to repress histone deacetylase 4 (HDAC4) and to promote differentiation of myoblasts (Chen et al., 2006). HDAC4 is highly abundant in mouse brain (Kumar et al., 2005) and its subcellular localization (nuclear or cytoplasmic) in rat hippocampal neurons is specified by neuronal activity (Chawla et al., 2003). Interestingly, Pandey et al. (2008) found that the anxiolytic effects produced by acute alcohol were associated with increased HDAC activity and reduced histone acetylation in the rat amygdala, and suggested that HDAC inhibitors may be potential therapeutic agents in treating alcohol withdrawal symptoms. Nevertheless, somewhat contradictorily, the Nestler group has reported that HDAC inhibition potentiates cocaine’s behavioral effects and that reducing acetylation through viral-mediated overexpression of HDAC4 in the NAc of mice decreased cocaine reward (Kumar et al., 2005). These authors also suggested that stimulation of gene transcription may be the predominant mechanism for cocaine-induced behavioral plasticity. These drug-specific or animal model-specific cellular activities and behaviors warn us about the potential risk of extrapolating results from one model into another, but also underscore the fine-tuning capabilities of these regulatory pathways.
