Ivy A S, Brunson K L, Sandman C, Baram T Z
Department of Anatomy/Neurobiology, University of California at Irvine, Irvine, CA 92697-4475, USA.
Neuroscience. 2008 Jun 26;154(3):1132-42. doi: 10.1016/j.neuroscience.2008.04.019. Epub 2008 May 22.
Early-life emotional stress may be associated with affective and cognitive disorders later in life, yet satisfactory animal models for studying the underlying mechanisms are limited. Because maternal presence and behavior critically influence molecular and behavioral stress responses in offspring, we sought to create a model of dysfunctional, fragmented maternal nurturing behavior that would, in turn, provoke chronic early-life stress in the offspring.
Sprague-Dawley rat dams' nursing and nurturing behaviors were altered by limiting their ability to create satisfactory nests during postpartum days 2-9. Maternal behavior was observed throughout the diurnal cycle, and the frequency and duration of nurturing behaviors were scored. In addition, potential stress and anxiety of the dams were assessed using behavioral, molecular and hormonal measures.
Both the quantity and the quality of dams' care of their pups were profoundly influenced by restriction of nesting materials in their cages: licking/grooming activities decreased and the frequency of leaving the pups increased, resulting in fragmented interactions between the dams and pups. The abnormal activity patterns of the dams were accompanied by increased anxiety-like behavior in the open field, but not in the elevated plus maze tests. Additionally, dams' plasma corticosterone levels and adrenal weights were augmented, suggesting chronic stress of these dams. By the end of the limited-nesting, stress-inducing period, hypothalamic corticotropin releasing hormone (CRH) mRNA expression was reduced in the limited-nesting dams, while arginine-vasopressin (AVP) mRNA levels were not significantly affected.
Limiting dams' ability to construct a nest for their pups leads to an abnormal repertoire of nurturing behaviors, possibly as a result of chronic stress and mild anxiety of the dams. Because the fragmented and aberrant maternal behavior provoked chronic stress in the pups, the limited-nesting paradigm provides a useful tool for studying the mechanisms and consequences of such early-life stress experience in the offspring.
生命早期的情绪应激可能与后期的情感和认知障碍有关,但用于研究潜在机制的理想动物模型有限。由于母鼠的存在和行为对后代的分子和行为应激反应有至关重要的影响,我们试图建立一种功能失调、碎片化的母性养育行为模型,进而引发后代慢性的生命早期应激。
在产后第2至9天,通过限制斯普拉格-道利大鼠母鼠建造适宜巢穴的能力,改变其哺乳和养育行为。在整个昼夜周期观察母性行为,并对养育行为的频率和持续时间进行评分。此外,采用行为、分子和激素指标评估母鼠潜在的应激和焦虑情况。
笼子中筑巢材料的限制对母鼠照顾幼崽的数量和质量均产生了深远影响:舔舐/梳理活动减少,离开幼崽的频率增加,导致母鼠与幼崽之间的互动碎片化。母鼠异常的活动模式伴随着旷场试验中类似焦虑行为的增加,但在高架十字迷宫试验中未出现这种情况。此外,母鼠的血浆皮质酮水平和肾上腺重量增加,表明这些母鼠处于慢性应激状态。在有限筑巢的应激诱导期结束时,有限筑巢组母鼠下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达降低,而精氨酸加压素(AVP)mRNA水平未受显著影响。
限制母鼠为幼崽筑巢的能力会导致养育行为异常,这可能是母鼠慢性应激和轻度焦虑的结果。由于这种碎片化和异常的母性行为会引发幼崽的慢性应激,有限筑巢范式为研究后代这种生命早期应激经历的机制和后果提供了一个有用的工具。