Gene expression changes caused by chronic drug exposure may also be mediated by regulatory RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Regulatory RNAs modify gene expression through multiple means, such as altering mRNA stability, basal transcription machinery, translational efficiency, and chromosome modification. miRNA array analysis in human prefrontal cortex revealed upregulation of approximately 35 miRNAs in alcoholics relative to controls with predicted target genes implicated in apoptosis, cell cycle, cell adhesion, nervous system development, and cell–cell signaling (Lewohl et al., 2011). Exposure of zebrafish embryos to cocaine reduced the expression of miR-133b in the CNS, and this difference in miR signaling might in turn modulate expression of dopamine receptors, the dopamine transporter, and tyrosine hydroxylase (Barreto-Valer, Lopez-Bellido, Macho Sanchez-Simon, & Rodriguez, 2012). The let-7 miR family may also interact with the 3′-untranslated region of μ-opioid receptor mRNA to regulate opioid tolerance (He & Wang, 2012). miRNAs are both synaptically enriched and depleted by drug exposure. Cocaine modulates levels of the miR-8 family which is enriched at postsynaptic densities and regulates expression of cell adhesion molecules (Eipper-Mains, Eipper,
