Global Effects of Heroin Self-Administration on microRNA Expression Profiles in Rat Brain

Gene expression and posttranscriptional regulation have been considered to play specific roles in heroin-induced compulsive seeking behavior and drug use. However, the roles of microRNAs (miRNAs), which are common posttranscriptional factors, in the molecular mechanisms of heroin addiction have received relatively little attention. In this study, microarray-based miRNA expression profiling was performed to investigate the deregulated miRNAs associated with heroin addiction in a self-administration paradigm. Furthermore, multiple algorithms for predicting the miRNA-binding sites identified numerous messenger RNA targets (n = 316) interacted with 27 differentially expressed miRNAs. Gene-set enrichment analysis identified 48 significantly overrepresented Gene Ontology terms, some of which were closely associated with neuronal network-related functions, including nervous system development, neuron projection, and negative regulation of synaptic transmission. These findings reveal the perturbed miRNAs in heroin self-administering rats and their interactions with related targets, providing novel insights into related molecular transcriptional regulation mechanisms and identifying promising candidates for clinical therapies against heroin addiction.