Chandrasekar and Dreyer identified another set of miRNAs (miR-181a, let-7d, and miR-124) whose expression is sensitive to cocaine (Chandrasekar and Dreyer, 2009). They found that chronic cocaine administration suppressed the expression of miR-124 and let-7d, but induced miR-181a in the mesolimbic dopaminergic system. The critical role of the mesolimbic dopaminergic system in addiction is well established (Koob and Volkow, 2010). In situ hybridization confirmed that the alterations in the expression of these miRNAs occurred in brain regions related to reward and memory. Further, in vitro overexpression of these miRNAs modulated the expression levels of proteins like BDNF and the dopamine D3 receptor, which have been heavily implicated in drug addiction (Heidbreder et al., 2005; Ghitza et al., 2010). In a subsequent study the same group also showed that in vivo modulation of these miRNAs in ventral striatum (nucleus accumbens) affects cocaine-induced place conditioning (Chandrasekar and Dreyer, 2011). These data show that cocaine can impact the expression of a range of different miRNAs depending on treatment and testing context, and support an important role for such miRNAs and their targeted mRNA transcripts in the development of drug addiction.
