Laboratory of Cognitive Neuroscience, Department of Physiology, National Defense Medical Center, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Physiology, National Defense Medical Center, Taipei, Taiwan.
Laboratory of Cognitive Neuroscience, Department of Physiology, National Defense Medical Center, Taipei, Taiwan.
Behav Brain Res. 2023 Sep 13;453:114613. doi: 10.1016/j.bbr.2023.114613. Epub 2023 Aug 6.
Stress is considered a crucial determinant influencing health capacity in modern society. Long-term stress makes individuals more susceptible to mental dysfunctions, among which depression and anxiety are two major mental disorders. The success of using selective serotonin reuptake inhibitors (SSRIs) to treat these two disorders highlights the involvement of the central serotonergic (5-HT) system. Later studies suggest both presynaptic and postsynaptic 5-HT profiles should be considered for the effects of SSRIs, making it difficult to interpret the etiological and therapeutic mechanisms underlying depression and anxiety. The present study aims to examine whether the intervention of escitalopram (Es, 5 mg/kg daily for 14 days) can reverse the behavioral phenotypes of both depression-like [by sucrose preference test (SPT) and forced swim test (FST)] and anxiety-like [by avoidance latency and escape latency in elevated-T maze (ETM)] behaviors, and the brain area-dependent neurochemical changes of 5-HT profiles of the terminal regions regarding both synaptic efflux and tissue levels in rats of chronic mild stress (CMS). Our results showed that: (i) Even mild stresses when presented in an unpredictable and long-term manner, can induce both depression-like and anxiety-like behaviors. (ii) Depressive profile indexed by SPT was more sensitive to reflect the Es effect than that of FST. (iii) Es did not significantly affect the CMS-induced anxiety-like symptoms indexed by ETM. (iv) Changes in the protein expression of 5-HT1A receptors in the prefrontal cortex and hippocampus were compatible with the treatment outcome. Our results contributed to the understanding of stress-induced mood dysfunction and the involvement of central 5-HT.
压力被认为是现代社会中影响健康能力的一个关键决定因素。长期的压力会使个体更容易出现精神功能障碍，其中抑郁和焦虑是两种主要的精神障碍。选择性 5-羟色胺再摄取抑制剂（SSRIs）成功地用于治疗这两种疾病，突出了中枢 5-羟色胺（5-HT）系统的参与。后来的研究表明，SSRIs 的作用应该同时考虑到突触前和突触后 5-HT 谱，这使得解释抑郁和焦虑的病因和治疗机制变得困难。本研究旨在探讨依他普仑（Es，每天 5mg/kg，连续 14 天）干预是否能逆转抑郁样（通过蔗糖偏好试验（SPT）和强迫游泳试验（FST））和焦虑样（通过高架十字迷宫试验（ETM）中的回避潜伏期和逃避潜伏期）行为以及慢性轻度应激（CMS）大鼠中与突触外排和组织水平相关的终端区域 5-HT 谱的脑区依赖性神经化学变化。我们的结果表明：（i）即使是在不可预测和长期的情况下出现的轻度压力，也会引起抑郁样和焦虑样行为。（ii）SPT 所反映的抑郁谱比 FST 更能敏感地反映 Es 的作用。（iii）Es 对 ETM 所反映的 CMS 诱导的焦虑样症状没有显著影响。（iv）前额叶皮层和海马体中 5-HT1A 受体的蛋白表达变化与治疗结果相吻合。我们的结果有助于理解应激诱导的情绪功能障碍和中枢 5-HT 的参与。
