Argonaute 2 in dopamine 2 receptor–expressing neurons regulates cocaine addiction

Anne Schaefer, Heh-In Im, Morten T. Venø, Christie D. Fowler, Alice Min, Adam Intrator, Jørgen Kjems, Paul Kenny, Donal O'Carroll, Paul Greengard
2010 Journal of Cell Biology  
Abbreviations used: ADCID, Argo2-dependent, induced by cocaine and DRD2-enriched; ANOVA, analysis of variance; miRNA, microRNA; MSN, medium spiny neuron; RISC, RNA-induced silencing complex; RQ, relative quantification; TH, tyrosine hydroxylase. Cocaine is a highly addictive drug that exerts its effects by increasing the levels of released dopamine in the striatum, followed by stable changes in gene transcription, mRNA translation, and metabolism within medium spiny neurons in the striatum. The
more » ... multiple changes in gene and protein expression associated with cocaine addiction suggest the existence of a mechanism that facilitates a coordinated cellular response to cocaine. Here, we provide evidence for a key role of miRNAs in cocaine addiction. We show that Argonaute 2 (Ago2), which plays an important role in miRNA generation and execution of miRNA-mediated gene silencing, is involved in regulation of cocaine addiction. Deficiency of Ago2 in dopamine 2 receptor (Drd2)-expressing neurons greatly reduces the motivation to self-administer cocaine in mice. We identified a distinct group of miRNAs that is specifically regulated by Ago2 in the striatum. Comparison of miRNAs affected by Ago2 deficiency with miRNAs that are enriched and/or up-regulated in Drd2-neurons in response to cocaine identified a set of miRNAs that are likely to play a role in cocaine addiction.
doi:10.1083/jcb1902oia4 fatcat:mgvzslwvabem3kxljynsriefcu