Antidepressant-like activity of L-701324 in mice: A behavioral and neurobiological characterization
| Autor: | Jie Zhao, Wen-Qian Tang, Ling Liu, Jiang-Hong Gu, Yue Liu, Yuan Wang, Bo Jiang, Chun-Hui Ji |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Neurogenesis Hippocampal formation Pharmacology Quinolones Hippocampus Receptors N-Methyl-D-Aspartate 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine Monoaminergic Medicine Animals 030304 developmental biology Brain-derived neurotrophic factor 0303 health sciences Behavior Animal business.industry Depression Brain-Derived Neurotrophic Factor Tail suspension test Antidepressive Agents Mice Inbred C57BL Disease Models Animal NMDA receptor Antidepressant business Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery Stress Psychological Behavioural despair test Signal Transduction |
| Zdroj: | Behavioural brain research. 399 |
| ISSN: | 1872-7549 |
| Popis: | Antidepressants currently used in clinical practice have limitations such as low efficacy, slow onset and various adverse reactions. It has become necessary to develop novel antidepressants beyond monoaminergic drugs. L-701,324 is a potent NMDA receptor antagonist, and the purpose of this study was to investigate the possible antidepressant effects of L-701,324 in mice. Here, various methods including the forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting and immunofluorescence, were used together. A single injection of L-701,324 exhibited antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated injection of L-701,324 not only prevented CUMS-induced depressive-like behaviors in mice, but also ameliorated the downregulating effects of CUMS on the hippocampal BDNF signaling cascade and neurogenesis. Furthermore, K252a, a potent inhibitor of the BDNF system, fully blocked the antidepressant-like activity of L-701,324 in mice. K252a administration also abolished the activating actions of L-701,324 on the hippocampal BDNF signaling cascade and neurogenesis in CUMS-treated mice. Collectively, these data indicated that L-701,324 possesses antidepressant-like activity in mice, which was mediated, at least in part, by promoting the hippocampal BDNF system. |
| Databáze: | OpenAIRE |
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