<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Chandrasekar, Vijay</dc:creator>
  <dc:creator>Dreyer, Jean-Luc</dc:creator>
  <dc:date>2011-02-09</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Molecular adaptations underlying drug seeking and relapse remain largely unknown. Studies highlight post-transcriptional modifications mediated by microRNAs (miRNAs) in addiction and other neurological disorders. We have previously shown that chronic cocaine suppresses miR-124 and let-7d and induces the expression of miR-181a in mesolimbic pathway. To further address the role and target gene regulation network of these miRNAs in vivo in cocaine addiction, we developed lentiviral vector (LV)-expressing miRNAs and their corresponding silencers for stable and regulatable miRNA expression. We tested in vivo miRNA gain and loss of function on cocaine-induced conditioned place preference (CPP) by localized LV-miRNA regulation in the nucleus accumbens (NAc). LV-miR-124 and let-7d expression in the NAc attenuates cocaine CPP, whereas LV-miR-181a enhances it. Silencing miRNAs by corresponding LV-miRNA silencers expressing perfect miRNA target sequences inversed this effect on cocaine CPP. Doxycycline treatment for switching off silencer expression abolished the observed behavioral changes. Behavioral changes mediated by LV-miRNA regulation resulted in dynamic alterations in transcription factors, receptors, and other effector genes involved in cocaine-induced plasticity. Our results describe a complex regulatory pathway mediated by miRNAs in cocaine-mediated neuronal adaptations.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/302239</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/302239/files/dre_raa.pdf</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/302239/files/dre_rml_sm.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1038/npp.2010.250</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>Neuropsychopharmacology. - 2011, vol. 36, p. 1149-1164</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">miRNA</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Cocaine</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Addiction</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Plasticity</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Lentivirus</dc:subject>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns6="xml" ns6:lang="en">Regulation of MiR-124, Let-7d, and MiR-181a in the accumbens affects the expression, extinction, and reinstatement of cocaine-induced conditioned place preference</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>