Acetylcholine (ACh) could be another neurotransmitter signaling pathway regulated by miRNAs in human alcoholic brains. miR-1 is a conserved muscle-specific microRNA that regulates aspects of both pre- and post-synaptic function at neuromuscular junctions (Simon et al., 2008). Using C. elegans as model system, Simon et al. (2008) demonstrated that miR-1 regulates the expression level of two nAChR subunits, thereby altering muscle sensitivity to ACh. Alcohol has been reported to enhance the function of naturally expressed α4β2 nAChRs and to inhibit the activity of naturally expressed α7 nAChRs (Narahashi et al., 1999). Furthermore, activation of nAChRs was reported to selectively reduce alcohol consumption in outbred Wistar rats (Dyr et al., 1999), while mutations in transmembrane domains of α2 channel subunits can enhance actions of alcohols on neuronal nicotinic receptors (Borghese et al., 2002).
