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The immobility time in tail suspension test (TST) and forced swim test (FST) was used to assess the antidepressant effects. Prior administration of L-arginine (750 mg\/kg, intraperitoneal [i.p.]), a NO synthase substrate that enhances NO signaling or sildenafil (5 mg\/kg, i.p.), a phosphodiesterase 5 inhibitor that enhances cGMP, blunted the antidepressant-like activity of YJ (2.7 g\/kg, i.g.). Co-treatment of ineffective dose of YJ (1.35 g\/kg, i.g.) with one of the reagents that suppress the NO\/cGMP signaling, including methylene blue (10 mg\/kg, i.p.), an inhibitor of NO synthase; 7-NI (7-nitroinidazole, 30 mg\/kg, i.p.), an nNOS specific inhibitor; L-NAME (10 mg\/kg, i.p.), a non-specific inhibitor of NO synthase; and MK-801 (0.05 mg\/kg, i.p.), an NMDA receptor antagonist, reduced the immobility time in TST and FST, compared with those in vehicle or single drug treatment groups. Neither above drugs alone or co-administrated with YJ affected locomotor activity or anxiety behavior in open field test. Thus, our results suggest that the antidepressant-like action of YJ may depend on the inhibition of NMDA\/NO\/cGMP pathway.<\/jats:p>","DOI":"10.1042\/bsr20190524","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T17:05:17Z","timestamp":1567098317000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NMDA receptors and L-arginine\/nitric oxide\/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice"],"prefix":"10.1042","volume":"39","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of Psychology, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Sheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Interdisciplinary Institute for Personalized Medicine in Brain Disorders, and Research Center for Formula and Syndromes, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-062X","authenticated-orcid":false,"given":"Wenda","family":"Xue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"2021111619483268800_B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1056\/NEJMra073096","article-title":"Major depressive disorder","volume":"358","author":"Belmaker","year":"2008","journal-title":"N. 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