Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice
Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 cha...
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| creator | Yang, Li-Ping Jiang, Fang-Jie Wu, Gui-Sheng Deng, Ke Wen, Meng Zhou, Xiaoju Hong, Xuechuan Zhu, Michael X Luo, Huai-Rong |
| description | Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research. |
| doi_str_mv | 10.1371/journal.pone.0136255 |
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Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136255</identifier><identifier>PMID: 26317356</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Animals ; Anti-Anxiety Agents - chemistry ; Anti-Anxiety Agents - pharmacology ; Antidepressants ; Antidepressive Agents - chemistry ; Antidepressive Agents - pharmacology ; Anxiety ; Anxiolytics ; Behavior ; Biosynthesis ; Body weight ; Brain ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - biosynthesis ; Channels ; Education ; Environmental stress ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene expression ; Inhibitors ; Kinases ; Laboratory animals ; Latency ; Light ; Male ; MAP Kinase Signaling System - drug effects ; Maze Learning - drug effects ; Mental depression ; Mental disorders ; Mice ; mRNA ; Neurogenesis ; Neurosciences ; Pharmaceutical sciences ; Phosphorylation ; Prefrontal cortex ; Prefrontal Cortex - metabolism ; Prefrontal Cortex - pathology ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Psychiatry ; Stress ; Stress, Psychological - drug therapy ; Stress, Psychological - metabolism ; Stress, Psychological - pathology ; Transient receptor potential proteins ; TRPC Cation Channels - antagonists & inhibitors ; TRPC Cation Channels - metabolism ; Virology</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0136255-e0136255</ispartof><rights>2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Yang et al 2015 Yang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-72b21a8062d713bb960a43d16c9344b2ae5fe5992f0ac7c7dde489e0db8ea77a3</citedby><cites>FETCH-LOGICAL-c526t-72b21a8062d713bb960a43d16c9344b2ae5fe5992f0ac7c7dde489e0db8ea77a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552833/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552833/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26317356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Li-Ping</creatorcontrib><creatorcontrib>Jiang, Fang-Jie</creatorcontrib><creatorcontrib>Wu, Gui-Sheng</creatorcontrib><creatorcontrib>Deng, Ke</creatorcontrib><creatorcontrib>Wen, Meng</creatorcontrib><creatorcontrib>Zhou, Xiaoju</creatorcontrib><creatorcontrib>Hong, Xuechuan</creatorcontrib><creatorcontrib>Zhu, Michael X</creatorcontrib><creatorcontrib>Luo, Huai-Rong</creatorcontrib><title>Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.</description><subject>AKT protein</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - chemistry</subject><subject>Anti-Anxiety Agents - pharmacology</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - chemistry</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Anxiety</subject><subject>Anxiolytics</subject><subject>Behavior</subject><subject>Biosynthesis</subject><subject>Body weight</subject><subject>Brain</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - biosynthesis</subject><subject>Channels</subject><subject>Education</subject><subject>Environmental stress</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Gene expression</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Latency</subject><subject>Light</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Maze Learning - drug effects</subject><subject>Mental depression</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>mRNA</subject><subject>Neurogenesis</subject><subject>Neurosciences</subject><subject>Pharmaceutical sciences</subject><subject>Phosphorylation</subject><subject>Prefrontal cortex</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Prefrontal Cortex - pathology</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Psychiatry</subject><subject>Stress</subject><subject>Stress, Psychological - drug therapy</subject><subject>Stress, Psychological - metabolism</subject><subject>Stress, Psychological - pathology</subject><subject>Transient receptor potential proteins</subject><subject>TRPC Cation Channels - antagonists & inhibitors</subject><subject>TRPC Cation Channels - metabolism</subject><subject>Virology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1vEzEUXCEQ_YB_gMASl1429ceuvXtBilYFIgWoUDhbXvtt47CxU9tb6L_HJWnVIk62xjPjN09TFG8InhEmyPnGT8GpcbbzDmaYME7r-llxTFpGS04xe_7oflScxLjBuGYN5y-LI8oZEazmx0Wc6ykBWgVQaQsuoV82rZFCX_0NjGj1_bKrzrsadWvlXAYWbm17m3xAl8GbSUNEc5esgV2AGFXWK2cy9Nv68TZZXS7tT0AXwwA6RWQd-mI1vCpeDGqM8PpwnhY_Pl6sus_l8tunRTdflrqmPJWC9pSoBnNqBGF933KsKmYI1y2rqp4qqAeo25YOWGmhhTFQNS1g0zeghFDstHi3992NPsrDvqIkAjdVQxvCM2OxZxivNnIX7FaFW-mVlX8BH66kCjnGCJIbmnesoDcUVyBIq6nRZugxGzLMdfb6cPht6rdgdF5mUOMT06cvzq7llb-RVV3ThrFscHYwCP56gpjk1kYN46gc-Gk_d4sxb0Wmvv-H-v901Z6lg48xwPAwDMHyrkP3KnnXIXnoUJa9fRzkQXRfGvYH_dHFmA</recordid><startdate>20150828</startdate><enddate>20150828</enddate><creator>Yang, Li-Ping</creator><creator>Jiang, Fang-Jie</creator><creator>Wu, Gui-Sheng</creator><creator>Deng, Ke</creator><creator>Wen, Meng</creator><creator>Zhou, Xiaoju</creator><creator>Hong, Xuechuan</creator><creator>Zhu, Michael X</creator><creator>Luo, Huai-Rong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150828</creationdate><title>Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice</title><author>Yang, Li-Ping ; Jiang, Fang-Jie ; Wu, Gui-Sheng ; Deng, Ke ; Wen, Meng ; Zhou, Xiaoju ; Hong, Xuechuan ; Zhu, Michael X ; Luo, Huai-Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-72b21a8062d713bb960a43d16c9344b2ae5fe5992f0ac7c7dde489e0db8ea77a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>AKT protein</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - chemistry</topic><topic>Anti-Anxiety Agents - pharmacology</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - chemistry</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Anxiety</topic><topic>Anxiolytics</topic><topic>Behavior</topic><topic>Biosynthesis</topic><topic>Body weight</topic><topic>Brain</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - biosynthesis</topic><topic>Channels</topic><topic>Education</topic><topic>Environmental stress</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Gene expression</topic><topic>Inhibitors</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Latency</topic><topic>Light</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Maze Learning - drug effects</topic><topic>Mental depression</topic><topic>Mental disorders</topic><topic>Mice</topic><topic>mRNA</topic><topic>Neurogenesis</topic><topic>Neurosciences</topic><topic>Pharmaceutical sciences</topic><topic>Phosphorylation</topic><topic>Prefrontal cortex</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Prefrontal Cortex - pathology</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Psychiatry</topic><topic>Stress</topic><topic>Stress, Psychological - drug therapy</topic><topic>Stress, Psychological - metabolism</topic><topic>Stress, Psychological - pathology</topic><topic>Transient receptor potential proteins</topic><topic>TRPC Cation Channels - antagonists & inhibitors</topic><topic>TRPC Cation Channels - metabolism</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Li-Ping</creatorcontrib><creatorcontrib>Jiang, Fang-Jie</creatorcontrib><creatorcontrib>Wu, Gui-Sheng</creatorcontrib><creatorcontrib>Deng, Ke</creatorcontrib><creatorcontrib>Wen, Meng</creatorcontrib><creatorcontrib>Zhou, Xiaoju</creatorcontrib><creatorcontrib>Hong, Xuechuan</creatorcontrib><creatorcontrib>Zhu, Michael X</creatorcontrib><creatorcontrib>Luo, Huai-Rong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Li-Ping</au><au>Jiang, Fang-Jie</au><au>Wu, Gui-Sheng</au><au>Deng, Ke</au><au>Wen, Meng</au><au>Zhou, Xiaoju</au><au>Hong, Xuechuan</au><au>Zhu, Michael X</au><au>Luo, Huai-Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-28</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0136255</spage><epage>e0136255</epage><pages>e0136255-e0136255</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26317356</pmid><doi>10.1371/journal.pone.0136255</doi><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Animals Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - pharmacology Antidepressants Antidepressive Agents - chemistry Antidepressive Agents - pharmacology Anxiety Anxiolytics Behavior Biosynthesis Body weight Brain Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - biosynthesis Channels Education Environmental stress Extracellular Signal-Regulated MAP Kinases - metabolism Gene expression Inhibitors Kinases Laboratory animals Latency Light Male MAP Kinase Signaling System - drug effects Maze Learning - drug effects Mental depression Mental disorders Mice mRNA Neurogenesis Neurosciences Pharmaceutical sciences Phosphorylation Prefrontal cortex Prefrontal Cortex - metabolism Prefrontal Cortex - pathology Proteins Proto-Oncogene Proteins c-akt - metabolism Psychiatry Stress Stress, Psychological - drug therapy Stress, Psychological - metabolism Stress, Psychological - pathology Transient receptor potential proteins TRPC Cation Channels - antagonists & inhibitors TRPC Cation Channels - metabolism Virology |
| title | Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T22%3A49%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Acute%20Treatment%20with%20a%20Novel%20TRPC4/C5%20Channel%20Inhibitor%20Produces%20Antidepressant%20and%20Anxiolytic-Like%20Effects%20in%20Mice&rft.jtitle=PloS%20one&rft.au=Yang,%20Li-Ping&rft.date=2015-08-28&rft.volume=10&rft.issue=8&rft.spage=e0136255&rft.epage=e0136255&rft.pages=e0136255-e0136255&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0136255&rft_dat=%3Cproquest_plos_%3E3793540461%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1708482816&rft_id=info:pmid/26317356&rft_doaj_id=oai_doaj_org_article_6d2136aebd204e719c2dcdfb03f36a6c&rfr_iscdi=true |