Several of the synaptically modulated miRNA families have been involved in the regulation of neurotransmitter signaling, which is mechanistically related to stimulation of reward circuits and the formation of associative, synapse-specific memories (Hyman et al., 2006). For example, the let-7 family, one of the miRNA families differentially expressed in PFC of human alcoholics, could be modulating the activity of a variety of neurotransmitter receptors. Several members of this family have been reported to regulate receptors such as the μ opioid receptor, the β2-adrenergic receptor, and the dopamine D3 receptor (Pillai, 2005; Chandrasekar and Dreyer, 2009; He et al., 2010). While investigating mechanisms contributing to opioid tolerance in mice, He et al. (2010) identified let-7 family members (let-7a, let-7c, and let-7g were used as representative members) as mediators of translocation and sequestration of μ opioid receptor mRNA into P-bodies, which led to translation repression without affecting the mRNA levels. A similar mechanism for repression of translational initiation of let-7 targets in human cells had previously been reported (Pillai, 2005). The μ opioid receptor is largely distributed along reward circuits, where it
