{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:15:12Z","timestamp":1777576512965,"version":"3.51.4"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7164290"],"award-info":[{"award-number":["7164290"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Our previous study showed that hypidone hydrochloride (YL-0919), a partial serotonin 1A (5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    ) receptor agonist and 5-HT reuptake inhibitor, exerts a significant antidepressant effect in various animal models. The aim of the present study was to further investigate the underlying mechanisms and whether it could act as a fast-onset antidepressant. In the current study, depressive-like behavior was induced in rats by a chronic unpredictable stress (CUS) model and assessed with the Sucrose Preference Test (SPT). Treatment with YL-0919 (2.5 mg\/kg, i.g.), but not with fluoxetine (Flx; 10 mg\/kg, i.g.), caused a fast improvement in the SPT scores. In CUS-exposed rats, YL-0919 treatment for 5 days decreased the immobility time in a forced swimming test (FST), and a 10-day treatment decreased the latency to feed in a Novelty-Suppressed Feeding Test (NSFT). In addition to the behavioral tests, the effects of YL-0919 on synaptic protein expression were also evaluated. Western blotting showed that YL-0919 significantly enhanced the expression levels of synaptic proteins such as synapsin I, postsynaptic density protein 95 (PSD95), phosphorylated mammalian targeting of rapamycin (pmTOR) and brain-derived neurotrophic factor (BDNF) in the hippocampus. To determine how the mTOR signaling is involved in the fast-onset antidepressant-like effects of YL-0919, the mTOR-specific inhibitor rapamycin was administered intracerebroventricularly (i.c.v.) together with the YL-0919 treatment. The observed changes in behavioral tests and protein expression could be reversed by rapamycin treatment. This suggests that the fast-onset antidepressant effects of YL-0919 were partially caused by changes in synaptogenesis mediated by activation of mTOR pathways. Our data suggest that YL-0919 may be a powerful\/effective antidepressant with fast-onset.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2018.00395","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T05:15:34Z","timestamp":1542690934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Hypidone Hydrochloride (YL-0919) Produces a Fast-Onset Reversal of the Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuhua","family":"Ran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengliang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youzhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.lfs.2014.02.014","article-title":"The role of mTOR in depression and antidepressant responses","volume":"101","author":"Abelaira","year":"2014","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1192\/bjp.bp.112.110650","article-title":"Antidepressant drugs and sexual dysfunction","volume":"202","author":"Baldwin","year":"2013","journal-title":"Br. 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