MiR-218 targets MeCP2 and inhibits heroin seeking behavior

• DOI: 10.1038/srep40413
• Publication Date: 2017-01-11T10:13:33Z
• Authors: Biao Yan; Zhaoyang Hu; Wenqing Yao; Qiumin Le; Bo Xu; Xing Liu; Lan Ma
• Keywords: Male; 0301 basic medicine; Neuronal Plasticity; Base Sequence; Methyl-CpG-Binding Protein 2; Substance-Related Disorders; Drug-Seeking Behavior; Lentivirus; Down-Regulation; Article; Nucleus Accumbens; 3. Good health; Heroin; Rats, Sprague-Dawley; MicroRNAs; 03 medical and health sciences; Animals; Humans; Gene Regulatory Networks; Reinforcement, Psychology

AbstractMicroRNAs (miRNAs) are a class of evolutionarily conserved, 18–25 nucleotide non-coding sequences that post-transcriptionally regulate gene expression. Recent studies implicated their roles in the regulation of neuronal functions, such as learning, cognition and memory formation. Here we report that miR-218 inhibits heroin-induced behavioral plasticity. First, network propagation-based method was used to predict candidate miRNAs that played potential key roles in regulating drug addiction-related genes. Microarray screening was also carried out to identify miRNAs responding to chronic heroin administration in the nucleus accumbens (NAc). Among the collapsed miRNAs, top-ranked miR-218 was decreased after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioned place preference (CPP) test and heroin self-administration experiments. Luciferase activity assay indicated that miR-218 could regulate 3′ untranslated regions (3′ UTR) of multiple neuroplasticity-related genes and directly target methyl CpG binding protein 2 (Mecp2). Consistently, Mecp2308/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, MeCP2, in the regulation of heroin-induced behavioral plasticity.