Third, the findings that AUD-associated brain miRNAs potentially target genes involved in addiction-linked pathways suggest that these miRNAs play a critical role in AUD development. Through miRNA target gene prediction and pathway enrichment analyses by DIANA-mirPath, we found that the majority of the 19 differentially expressed miRNAs (Table S2) identified in one or more of the eight brain regions could target coding genes (or mRNAs) that participate in neurobiological processes of drug reward or addiction (Fig. 3). Among the top 14 pathways, four were related to drug addiction (Morphine Addition, Retrograde Endocannabinoid Signaling, Cocaine Addiction, and Amphetamine Addiction) and two were related to synaptic functions (GABAergic Synapse and Glutamatergic Synapse). Although alcohol and drugs of abuse (e.g., morphine and cocaine) possess diverse neuropharmacological potentials, their reinforcing effects are mediated by common pathways (such as dopaminergic and glutamatergic pathways) via the activation of the mesocorticolimbic system that are mainly comprised of the AMY, the NAc, the PFC, and the VTA [45]. That is to say, the above pathways for drug addiction or synaptic function can also mediate the rewarding effect of
