Lab. of Clinical and Translational Studies, NIAAA, NIH, Bethesda, MD, 20817, United States.
Department of Psychology, Colby College, Waterville, ME, 04901, United States.
Behav Brain Res. 2021 Feb 26;400:113028. doi: 10.1016/j.bbr.2020.113028. Epub 2020 Dec 9.
Exposure to traumatic events during childhood increases the risk of adult psychopathology, including anxiety, depression, alcohol use disorders and their co-morbidity. Early life trauma also results in increased symptom complexity, treatment resistance and poor treatment outcomes. The purpose of this study was to establish a novel rodent model of adolescent stress, based on an ethologically relevant life-threatening event, live predator exposure. Rats were exposed to a live predator for 10 min. at three different time points (postnatal day (PND)31, 46 and 61). Adult depression-, anxiety-like behaviors and ethanol consumption were characterized well past the last acute stress event (two weeks). Behavioral profiles across assessments were developed to characterize individual response to adolescent stress. CNS activation patterns in separate groups of subjects were characterized after the early (PND31) and last predator exposure (PND61). Subjects exposed to live-predator adolescent stress generally exhibited less exploratory behavior, less propensity to venture into open spaces, a decreased preference for sweet solutions and decreased ethanol consumption in a two-bottle preference test. Additional studies demonstrated blunted cortisol response and CNS activation patterns suggestive of habenula, rostromedial tegmental (RMTg), dorsal raphe and central amygdala involvement in mediating the adult consequences of adolescent stress. Thus, adolescent stress in the form of live-predator exposure results in significant adult behavioral and neurobiological disturbances. Childhood trauma, its impact on neurodevelopment and the subsequent development of mood disorders is a pervasive theme in mental illness. Improving animal models and our neurobiological understanding of the symptom domains impacted by trauma could significantly improve treatment strategies.
儿童时期经历创伤性事件会增加成年后出现精神病理学的风险，包括焦虑、抑郁、酒精使用障碍及其共病。早期生活创伤还会导致症状复杂性增加、治疗抵抗和治疗效果不佳。本研究的目的是建立一种新的基于与行为相关的危及生命事件，即活捕食者暴露的青少年应激的啮齿动物模型。将大鼠在三个不同时间点（出生后第 31 天、46 天和 61 天）暴露于活捕食者中 10 分钟。在最后一次急性应激事件（两周后）后，仍可很好地描述成年期的抑郁、焦虑样行为和乙醇消耗。为了描述个体对青少年应激的反应，制定了跨评估的行为特征。在单独的受试组中，在早期（PND31）和最后一次捕食者暴露（PND61）后，对中枢神经系统激活模式进行了特征描述。一般来说，经历过青少年应激的大鼠表现出较少的探索行为，较少冒险进入开阔空间，对甜味溶液的偏好降低，在双瓶偏好测试中乙醇消耗减少。进一步的研究表明，应激激活的下丘脑外侧核（LHb）、中脑腹内侧区（RMTg）、中缝背核（DRN）和中央杏仁核（CeA）等脑区参与了青少年应激对成年的影响，这些脑区的皮质醇反应和激活模式都变迟钝。因此，活捕食者暴露导致的青少年应激会导致显著的成年行为和神经生物学紊乱。童年创伤及其对神经发育的影响，以及随后情绪障碍的发展，是精神疾病中的一个普遍主题。改善动物模型和我们对创伤影响的神经生物学理解，可以显著改善治疗策略。
