PMID- 25330738 OWN - NLM STAT- MEDLINE DCOM- 20160801 LR - 20220309 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 20 IP - 10 DP - 2015 Oct TI - MicroRNA-30a-5p in the prefrontal cortex controls the transition from moderate to excessive alcohol consumption. PG - 1219-31 LID - 10.1038/mp.2014.120 [doi] AB - MicroRNAs (miRNAs) induce messenger RNA (mRNA) degradation and repress mRNA translation. Several miRNAs control the expression of the brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC). The BDNF signaling pathway is activated by moderate intake of alcohol to prevent escalation to excessive drinking. Here, we present data to suggest that the transition from moderate to uncontrolled alcohol intake occurs, in part, upon a breakdown of this endogenous protective pathway via a miRNA-dependent mechanism. Specifically, a mouse paradigm that mimics binge alcohol drinking in humans produced a robust reduction in BDNF mRNA levels in the medial PFC (mPFC), which was associated with increased expression of several miRNAs including miR-30a-5p. We show that miR-30a-5p binds the 3' untranslated region of BDNF, and that overexpression of miR-30a-5p in the mPFC decreased BDNF expression. Importantly, overexpression of miR-30a-5p in the mPFC produced an escalation of alcohol intake and a preference over water. Conversely, inhibition of miR-30a-5p in the mPFC using a Locked Nucleic Acid sequence that targets miR-30a-5p restored BDNF levels and decreased excessive alcohol intake. Together, our results indicate that miR-30a-5p plays a key role in the transition from moderate to excessive alcohol intake. FAU - Darcq, E AU - Darcq E AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Warnault, V AU - Warnault V AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Phamluong, K AU - Phamluong K AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Besserer, G M AU - Besserer GM AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Liu, F AU - Liu F AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. FAU - Ron, D AU - Ron D AD - Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. LA - eng GR - P50 AA017072/AA/NIAAA NIH HHS/United States GR - R01 AA016848/AA/NIAAA NIH HHS/United States GR - R37 AA016848/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141021 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MicroRNAs) RN - 0 (Mirn30d microRNA, mouse) RN - 0 (RNA, Messenger) SB - IM EIN - Mol Psychiatry. 2015 Oct;20(10):1261. PMID: 25385365 MH - Alcohol Drinking/*genetics/metabolism MH - Alcoholic Intoxication/*genetics/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/metabolism MH - Prefrontal Cortex/metabolism/*physiology MH - RNA, Messenger/genetics/metabolism PMC - PMC4437888 MID - NIHMS686464 COIS- Conflict of Interest: The authors declare no conflict of interest. EDAT- 2014/10/22 06:00 MHDA- 2016/08/02 06:00 PMCR- 2015/10/01 CRDT- 2014/10/22 06:00 PHST- 2014/02/03 00:00 [received] PHST- 2014/08/11 00:00 [revised] PHST- 2014/08/25 00:00 [accepted] PHST- 2014/10/22 06:00 [entrez] PHST- 2014/10/22 06:00 [pubmed] PHST- 2016/08/02 06:00 [medline] PHST- 2015/10/01 00:00 [pmc-release] AID - mp2014120 [pii] AID - 10.1038/mp.2014.120 [doi] PST - ppublish SO - Mol Psychiatry. 2015 Oct;20(10):1219-31. doi: 10.1038/mp.2014.120. Epub 2014 Oct 21.