Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Dec 20;127:110825. doi: 10.1016/j.pnpbp.2023.110825. Epub 2023 Jul 10.
The interplay of social, psychological, and biological stresses can trigger mental health conditions such as major depressive disorder (MDD), adjustment disorder, and posttraumatic stress disorder (PTSD). The endocannabinoid system (ECS), comprising endocannabinoids and cannabinoid receptors, is the critical pathway that mediates responses to stress stimuli. This study aimed to investigate the ECS's impact on responding to chronic social instability stress (SIS). Wistar (WIS) rats and an endogenously depressed rat model, Wistar-Kyoto (WKY), were used to evaluate depression- and anxiety-like behavioral responses, cognitive function, hormone levels, and ECS function. The animals in the stress group (WIS-STS and WKY-STS) were exposed to TMT (predator odor) for 10 mins (two exposures in total: one in light cycle and one in dark cycle) and daily roommate changes (30 days in total), while the control group (CTL) rats were exposed to a sham odor stimulus (distilled water) and did not undergo roommate changes. The results in the open field test suggest that WKY rats had significantly lower locomotor activity than WIS rats. In contrast, WKY rats and chronically stressed WIS rats presented similar depression- and anxiety-like behaviors and impaired cognitive function in the elevated plus maze, forced swimming test, and novel objective recognition test. However, chronic SIS did not exacerbate these behavioral changes in WKY rats. ELISA and Western blot analysis indicated that chronic SIS did not induce further upregulation of endocannabinoids and CBR downregulation in WKY rats compared to WIS rats. In addition, the Luminex assay revealed that WKY rats showed a higher resilience on the HPA-axis modulation towards chronic SIS, distinguished by the hyperactivity of the HPA-axis modulation in WIS rats. Overall, the study revealed that the chronic SIS animal model (stressed WIS rats) and an animal model of endogenous depression (WKY rats) can generate similar behavioral changes in anxious behavior, behavioral despair, and cognitive impairment. Both animal models present hyperactivity of the ACTH modulation and ECS activity, while WKY rats are more resilient on CORT modulation towards chronic SIS.
社会、心理和生物压力的相互作用会引发心理健康问题，如重度抑郁症（MDD）、适应障碍和创伤后应激障碍（PTSD）。内源性大麻素系统（ECS）由内源性大麻素和大麻素受体组成，是介导应激刺激反应的关键途径。本研究旨在探讨 ECS 对慢性社会不稳定应激（SIS）反应的影响。使用 Wistar（WIS）大鼠和内源性抑郁大鼠模型 Wistar-Kyoto（WKY）评估抑郁和焦虑样行为反应、认知功能、激素水平和 ECS 功能。应激组（WIS-STS 和 WKY-STS）的动物暴露于 TMT（捕食者气味）10 分钟（总共两次暴露：一次在光照周期，一次在暗周期）和每天室友变化（总共 30 天），而对照组（CTL）大鼠暴露于假气味刺激（蒸馏水），并且不进行室友变化。旷场试验的结果表明，WKY 大鼠的运动活性明显低于 WIS 大鼠。相比之下，WKY 大鼠和慢性应激 WIS 大鼠在高架十字迷宫、强迫游泳试验和新的客观识别试验中表现出相似的抑郁和焦虑样行为以及认知功能障碍。然而，慢性 SIS 并没有加重 WKY 大鼠的这些行为变化。ELISA 和 Western blot 分析表明，与 WIS 大鼠相比，慢性 SIS 并没有进一步上调 WKY 大鼠的内源性大麻素和 CBR 下调。此外，Luminex 测定表明，WKY 大鼠在 HPA 轴调节方面对慢性 SIS 表现出更高的弹性，WIS 大鼠的 HPA 轴调节过度活跃。总体而言，该研究表明，慢性 SIS 动物模型（应激 WIS 大鼠）和内源性抑郁动物模型（WKY 大鼠）可在焦虑行为、行为绝望和认知障碍方面产生相似的行为变化。两种动物模型均表现出 ACTH 调节和 ECS 活性过度活跃，而 WKY 大鼠在 CORT 调节方面对慢性 SIS 更具弹性。
