title: Prolonged Induction of miR-212/132 and REST Expression in Rat Striatum Following Cocaine Self-Administration.
abstract: Chronic exposure to cocaine in vivo induces long-term synaptic plasticity associated with the brain's circuitry that underlies development of repetitive and automatic behaviors called habits. In fact, prolonged drug consumption results in aberrant expression of protein-coding genes and small regulatory RNAs, including miRNAs that are involved in synaptic plasticity and neuroadaptations. However, the mechanisms mediating cocaine use disorder are still not fully understood. The present study is designed to examine the expression of miR-124, miR-132, miR-134, and miR-212, as well as the levels of the Ago2, Pum2, and REST mRNAs and proteins implicated in their regulation. We applied rat cocaine self-administration (SA) and extinction training procedures with a yoked triad to assess the changes in the levels of four miRNAs and three protein-coding genes and corresponding proteins in the dorsal striatum. We demonstrated that elevated expression of mature miR-212 and miR-132 is long-lasting and persists in the drug-free period (till 10-day abstinence). Moreover, mRNA and protein of REST, a regulator of neuronal transcription, was raised selectively in cocaine self-administering rats and Ago2 transcript decreased after cocaine treatment. Unexpectedly, the expression level of Ago2 and Pum2 proteins changed only in the active cocaine-receiving animals. These results point out the important aspects of long-lasting alterations in microRNAs, genes, and protein expressions involved in the control of synaptic plasticity associated with reward and motivation learning related to cocaine addiction.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. annasc@if-pan.krakow.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Sadakierska-Chudy
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frankowska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Miszkiel
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wydra
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jastrzębska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics*; D017072:Neostriatum / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012646:Self Administration; D000099229:RE1-Silencing Transcription Factor
chemical_list: D003042:Cocaine; D035683:MicroRNAs; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C548821:MIRN132 microRNA, rat; C552427:MIRN212 microRNA, rat
keywords: Addiction; Cocaine self-administration; Extinction training; Gene expression; Striatum; Synaptic proteins; miRNAs