Up-regulated miRNAs in the frontal cortex of alcoholics are also involved in behavioral modifications that occur during the addiction cycle and in other neuropsychiatric disorders. For instance, miR-339 is up-regulated in the frontal cortex of alcoholics and in patients with anxiety disorders (Malan-Muller et al., 2013; Nunez and Mayfield, 2012). Target predicting software proposed adenosine receptor A2a (ADORA2A), brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone receptor 2 (CRHR2), and sodium-dependent noradrenaline transporter (SLC6A2) as possible targets of miR-339 (Malan-Muller et al., 2013). CRHR2 and BDNF have both been implicated in stress disorders and AUD (Moonat and Pandey, 2012; Spence et al., 2009). Thus, miR-339 may be important for anxiety-like behaviors associated with the addiction cycle. miR-152 is up-regulated in the frontal cortex of human alcoholics but down-regulated in depressed individuals (Nunez and Mayfield, 2012; Smalheiser et al., 2014). A predicted target of miR-152 is ADAM17, a protein critical for processing of TNFα at the cell surface (Su et al., 2014). The role of TNFα and neuroimmune signaling in AUD suggests a potential neuroimmune function for miR-152. These studies support the overall hypothesis that miRNAs regulate important behavioral aspects of addiction and other psychiatric disorders.
