Manz Kevin M, Levine Wendy A, Seckler Joshua C, Iskander Anthony N, Reich Christian G
a Program in Psychology , Ramapo College of New Jersey , Mahwah , NJ , USA.
Stress. 2018 Mar;21(2):169-178. doi: 10.1080/10253890.2017.1423285. Epub 2018 Jan 8.
Psychosocial stress is linked to the etiology of several neuropsychiatric disorders, including Major Depressive Disorder and Post-Traumatic-Stress-Disorder. Adolescence is a critical neurobehavioral developmental period wherein the maturing nervous system is sensitive to stress-related psychosocial events. The effects of social defeat stress, an animal model of psychosocial stress, on adolescent neurobehavioral phenomena are not well explored. Using the standard Resident-Intruder-Paradigm (RIP), adolescent Long-Evans (LE, residents, n = 100) and Sprague-Dawley (SD, intruders, n = 100) rats interacted for five days to invoke chronic social stress. Tests of depressive behavior (forced-swim-test (FST)), fear conditioning, and long-term synaptic plasticity are affected in various adult rodent chronic stress models, thus we hypothesized that these phenomena would be similarly affected in adolescent rats. Serendipitously, we observed the Intruders became the dominant rats and the Residents were the defeated/submissive rats. This robust and reliable role-reversal resulted in defeated LE-Residents showing a depressive-like state (increased time spent immobile in the FST), enhanced fear conditioning in both hippocampal-dependent and hippocampal-independent fear paradigms and altered hippocampal long-term synaptic plasticity, measured electrophysiologically in vitro in hippocampal slices. Importantly, SD-Intruders, SD and LE controls did not significantly differ from each other in any of these assessments. This reverse-Resident-Intruder-Paradigm (rRIP) represents a novel animal model to study the effects of stress on adolescent neurobehavioral phenomenon.
心理社会应激与多种神经精神疾病的病因有关，包括重度抑郁症和创伤后应激障碍。青春期是一个关键的神经行为发育时期，在此期间，成熟的神经系统对与应激相关的心理社会事件敏感。社会挫败应激作为心理社会应激的一种动物模型，其对青少年神经行为现象的影响尚未得到充分研究。使用标准的居住者-入侵者范式（RIP），青春期的长 Evans（LE，居住者，n = 100）和斯普拉格-道利（SD，入侵者，n = 100）大鼠相互作用五天以引发慢性社会应激。在各种成年啮齿动物慢性应激模型中，抑郁行为测试（强迫游泳测试（FST））、恐惧条件反射和长期突触可塑性都会受到影响，因此我们假设这些现象在青春期大鼠中也会受到类似影响。意外的是，我们观察到入侵者变成了占主导地位的大鼠，而居住者则是被击败/顺从的大鼠。这种强大且可靠的角色逆转导致被击败的 LE 居住者表现出类似抑郁的状态（在 FST 中不动时间增加），在海马依赖性和海马非依赖性恐惧范式中恐惧条件反射增强，并且改变了海马长期突触可塑性，这是在海马切片中通过体外电生理测量的。重要的是，SD 入侵者、SD 和 LE 对照组在任何这些评估中彼此之间均无显著差异。这种反向居住者-入侵者范式（rRIP）代表了一种研究应激对青少年神经行为现象影响的新型动物模型。
