Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA.
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:80-87. doi: 10.1016/j.pnpbp.2017.10.013. Epub 2017 Oct 24.
Earlier, we have reported that post-traumatic stress disorder (PTSD)-like behaviors developed in rats that witnessed their cage mates undergo repeated traumatic stress. More recently, we published that early life physical traumatic stress leads to later life depression-like behaviors in rats. Whether early life trauma witness causes later life PTSD-like behaviors is not known. Also unclear are sex-specific stress-induced behavioral variations in later life. The early life witness component of stress is an important aspect of stress-induced psychopathologies and must be investigated.
Here, we have examined the impact of early life repeated witnessing of traumatic events by pups from post-natal day (PND) 21-PND27, on later life behaviors at PND60, and the behavioral impact of postpartum traumatic stress in female rats.
We used a modified version of rodent social defeat model to induce postpartum stress in female rats and trauma witness stress in pups. One female Sprague-Dawley rat (intruder) was introduced into the cage of an aggressive Long-Evans male rat (resident). The encounter between the two resulted in attacks between the female rat and the Long-Evans male rat. Three exposures of social defeat (attacks) were given for 7 consecutive days. The social defeat traumatic events were witnessed by 6 pups (offspring of the intruder female rat, PND21-27), placed in six separate enclosures surrounding the cage. The objective of this experiment was three-fold: 1) to test later life behavioral effects in pups from witnessing maternal defeat, 2) to examine gender susceptibility of pups in maternal defeat witness-induced behaviors, 3) to test behavioral effect in female rats 24h after receiving the last social defeat exposure.
We observed that while anxiety-like behavior assessed in open-field and elevated plus-maze tests, was not affected in male or female rats upon witnessing repeated maternal traumatic stress, depression-like behavior in forced-swim test was observed at PND60 in both male and female rats, with greater effect in male rats. No change was observed in learning and memory functions using radial arm water maze test in both male and female rats. Interestingly, socially defeated female rats (dams: mother of the pups) developed both anxiety and depression-like behavior with no change in learning-memory function when compared to control female rats.
Our findings suggest that early life maternal stress witness history leads to depression-like behavior in both male and female adult rats, and dams developed both anxiety and depression-like behaviors.
早前，我们曾报道过，目击笼中同伴反复遭受创伤应激的大鼠会出现创伤后应激障碍（PTSD）样行为。最近，我们发表的文章指出，早期生活中的躯体创伤性应激会导致大鼠在以后的生活中出现抑郁样行为。早期生活中的创伤目击是否会导致以后生活中的 PTSD 样行为尚不清楚。此外，后期生活中性别特异性应激诱导的行为变化也不清楚。应激的早期生活目击成分是应激引起的精神病理学的一个重要方面，必须进行研究。
在这里，我们研究了从出生后第 21 天到第 27 天（PND21-PND27）的幼鼠反复目睹创伤性事件的早期生活对 PND60 后生活行为的影响，以及产后创伤应激对雌性大鼠的行为影响。
我们使用改良版的啮齿动物社交挫败模型，在雌性大鼠中诱导产后应激，并在幼鼠中诱导创伤目击应激。一只雌性斯普拉格-道利（Sprague-Dawley）大鼠（入侵者）被引入一只攻击性的长耳大（Long-Evans）雄性大鼠（居民）的笼子里。两者之间的相遇导致雌性大鼠和长耳大雄性大鼠之间的攻击。连续 7 天进行 3 次社交挫败（攻击）。6 只幼鼠（入侵者雌性大鼠的后代，PND21-27）目睹了社交挫败创伤事件，它们被放置在笼子周围的 6 个单独的围栏中。这个实验的目的有三个：1）测试幼鼠目睹母体挫败后的后期生活行为影响，2）测试母体挫败目击诱导行为中幼鼠的性别易感性，3）测试雌性大鼠在接受最后一次社交挫败暴露后 24 小时的行为影响。
我们观察到，虽然在旷场和高架十字迷宫测试中评估的焦虑样行为在雄性或雌性大鼠中没有受到影响，但在强迫游泳测试中观察到的抑郁样行为在雄性和雌性大鼠中都在 PND60 时出现，雄性大鼠的影响更大。在雄性和雌性大鼠的放射臂水迷宫测试中，均未观察到学习和记忆功能的变化。有趣的是，与对照组雌性大鼠相比，社交挫败的雌性大鼠（母鼠：幼鼠的母亲）发展出焦虑和抑郁样行为，而学习记忆功能没有变化。
我们的研究结果表明，早期生活中的母体应激目击史会导致雄性和雌性成年大鼠出现抑郁样行为，而母鼠会出现焦虑和抑郁样行为。
