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- Title
The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919).
- Authors
Sun, Li-jun; Zhang, Li-ming; Liu, Dan; Xue, Rui; Liu, Yan-qin; Li, Lei; Guo, Ying; Shang, Chao; Yao, Jun-qi; Zhang, You-zhi; Li, Yun-feng
- Abstract
Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.
- Subjects
CORTISONE; PYRAMIDAL neurons; DENDRITIC spines; ANTIDEPRESSANTS; ADRENOCORTICOTROPIC hormone; PREFRONTAL cortex; SEROTONIN antagonists
- Publication
Metabolic Brain Disease, 2019, Vol 34, Issue 5, p1375
- ISSN
0885-7490
- Publication type
Article
- DOI
10.1007/s11011-019-00439-8