title: MiR-218 targets MeCP2 and inhibits heroin seeking behavior.
abstract: MicroRNAs (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/ymice 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.
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yao
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Le
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and The Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation / Q000235:genetics; D058999:Drug-Seeking Behavior; D053263:Gene Regulatory Networks; D003932:Heroin / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D019966:Substance-Related Disorders / Q000235:genetics
chemical_list: C000628521:MIRN218 microRNA, rat; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D003932:Heroin