Taken together, our analysis of potential effects of alcohol-responsive miRNAs on neurotransmitter receptor-mediated signaling indicates that a variety of neurotransmitter-regulated pathways may be simultaneously changing in response to alcohol as well as other drugs of abuse, and that the activity of multiple key miRNA families may be contributing to this particular complex network of interactions. Direct effect of upregulated miRNAs (as in the cohort of human alcoholic studied by Lewohl et al., 2011) over their putative neurotransmitter receptor targets is suggestive of a neuroadaptive response to counteract the drug-induced receptor activation characteristic in multiple types of addiction. On the other hand, since receptor endocytosis contributes to signal termination and desensitization of activated G protein-coupled receptors (Finn and Whistler, 2001; Li and van der Vaart, 2011), miRNA-driven downregulation of dynamin-1, which disrupts neurotransmitter receptor endocytosis, might contribute to the addictive effects of alcohol as well as other drugs of abuse.
