PMID- 22890078 OWN - NLM STAT- MEDLINE DCOM- 20130501 LR - 20161125 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 223 DP - 2012 Oct 25 TI - Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine produces antidepressant effects in rats: role of brain-derived neurotrophic factor. PG - 219-24 LID - S0306-4522(12)00830-5 [pii] LID - 10.1016/j.neuroscience.2012.08.010 [doi] AB - Recent studies highlight that the brain glutamate system is involved in the etiology of depression and glutamatergic-targeting drugs are currently being explored as novel antidepressant medications. Previous studies reveal that the selective metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) produces antidepressant-like effects in behavioral despair and olfactory bulbectomy models. The current study aimed to further explore its behavioral actions in additional animal models of depression (forced swimming test (FST) and learned helplessness (LH) test) and its underlying neurobiological mechanisms. The results demonstrated that acute treatment of MPEP at 30 but not 10mg/kg significantly reduced immobility in FST without affecting locomotor activities. Sub-chronic, five-day treatment of MPEP (30 mg/kg) decreased escape failures in animals that had developed LH symptoms. This sub-chronic treatment also increased hippocampal brain-derived neurotrophic factor (BDNF) protein levels in both non-stressed and stressed animals and restored the stress-induced down-regulation of BDNF expression. Current findings provide strong evidence for further studies of MPEP as a tool to explore novel antidepressants. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Liu, C Y AU - Liu CY AD - Department of Neurosurgery, The Third Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China. FAU - Jiang, X X AU - Jiang XX FAU - Zhu, Y H AU - Zhu YH FAU - Wei, D N AU - Wei DN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120811 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Pyridines) RN - 7VC0YVI27Y (6-methyl-2-(phenylethynyl)pyridine) SB - IM MH - Analysis of Variance MH - Animals MH - Antidepressive Agents/pharmacology/*therapeutic use MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Depression/*drug therapy MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Down-Regulation/*drug effects MH - Escape Reaction/drug effects MH - Helplessness, Learned MH - Immobility Response, Tonic/drug effects MH - Male MH - Motor Activity/drug effects MH - Olfactory Bulb/surgery MH - Pyridines/pharmacology/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Swimming/psychology EDAT- 2012/08/15 06:00 MHDA- 2013/05/02 06:00 CRDT- 2012/08/15 06:00 PHST- 2012/05/26 00:00 [received] PHST- 2012/07/17 00:00 [revised] PHST- 2012/08/06 00:00 [accepted] PHST- 2012/08/15 06:00 [entrez] PHST- 2012/08/15 06:00 [pubmed] PHST- 2013/05/02 06:00 [medline] AID - S0306-4522(12)00830-5 [pii] AID - 10.1016/j.neuroscience.2012.08.010 [doi] PST - ppublish SO - Neuroscience. 2012 Oct 25;223:219-24. doi: 10.1016/j.neuroscience.2012.08.010. Epub 2012 Aug 11.