PMID- 23601049 OWN - NLM STAT- MEDLINE DCOM- 20140123 LR - 20191210 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 38 IP - 2 DP - 2013 Jul TI - Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption. PG - 2328-37 LID - 10.1111/ejn.12228 [doi] AB - Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. CI - (c) 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Bahi, Amine AU - Bahi A AD - Department of Anatomy, Tawam Medical Campus, CMHS, United Arab Emirates University, Al Ain, UAE. amine.bahi@uaeu.ac.ae FAU - Dreyer, Jean-Luc AU - Dreyer JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130419 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN124 microRNA, rat) RN - 0 (MicroRNAs) RN - 3K9958V90M (Ethanol) SB - IM MH - Alcohol Drinking/blood/genetics/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism/pharmacology MH - Conditioning, Psychological/drug effects MH - Corpus Striatum/*metabolism MH - Ethanol MH - Genetic Vectors MH - Lentivirus/genetics MH - Male MH - MicroRNAs/genetics/*metabolism/pharmacology MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - BDNF OT - conditioned place preference OT - lentiviral vector OT - miR124a OT - microRNA OT - siRNA EDAT- 2013/04/23 06:00 MHDA- 2014/01/24 06:00 CRDT- 2013/04/23 06:00 PHST- 2012/11/12 00:00 [received] PHST- 2013/03/21 00:00 [revised] PHST- 2013/03/22 00:00 [accepted] PHST- 2013/04/23 06:00 [entrez] PHST- 2013/04/23 06:00 [pubmed] PHST- 2014/01/24 06:00 [medline] AID - 10.1111/ejn.12228 [doi] PST - ppublish SO - Eur J Neurosci. 2013 Jul;38(2):2328-37. doi: 10.1111/ejn.12228. Epub 2013 Apr 19.