Cabrera R J, Rodríguez-Echandía E L, Jatuff A S, Fóscolo M
Laboratorio de Investigaciones Cerebrales and Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Braz J Med Biol Res. 1999 Oct;32(10):1229-37. doi: 10.1590/s0100-879x1999001000009.
Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; chi2 test, P<0.05) and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model.
早期刺激已被证明在许多物种中会产生持久影响。产前暴露于一些强烈应激源可能会影响神经系统的发育，导致成年后出现行为障碍。本研究的目的是探讨孕期大鼠暴露于可变轻度应激下的产后有害影响。雌性霍尔兹曼大鼠在孕期每天接受一次慢性可变应激（CVS）（产前应激；PS组）。对照孕鼠（C组）不受干扰。PS和C组母鼠的幼崽在出生后48小时称重并分为两组。一组与自己的母鼠一起饲养（PS组，N = 70；C组，N = 36），而另一组PS幼崽与C组母鼠交叉寄养（PSF组，N = 47），另一组C组幼崽与PS组母鼠交叉寄养（CF组，N = 58）。幼崽在断奶前（出生后第28天）不受干扰。雄性后代在动物活动监测仪中进行运动活动测试（第28天）、丰富环境测试（第37天）和社交互动测试（第42天）。在第2天、第28天和第60天记录体重。PS组幼崽的出生体重低于C组幼崽（邓肯检验，P<0.05）。与应激母鼠一起哺乳的PS组幼崽断奶前死亡率更高（C组：23%，PS组：60%；卡方检验，P<0.05），并且在第28天和第60天体重低于对照组（邓肯检验，分别为P<0.05和P<0.01）。在第28天测试时，PS组、PSF组和CF组的运动活动得分低于对照组（邓肯检验，PS组P<0.01，CF组和PSF组P<0.05）。在第37天进行的丰富环境测试中，未检测到组间总运动活动的差异；然而，PS组、CF组和PSF组的探索时间比对照组少（邓肯检验，P<0.05）。只有PS组在第42天显示运动活动受损和社交行为受损（邓肯检验，P<0.05）。事实上，孕期CVS处理加上与先前应激的母鼠一起哺乳会导致大鼠出现持久的身体和行为变化。将暴露于PS的幼崽交叉寄养到未受应激的母鼠可抵消该处理的大部分有害影响。产前应激加上与先前应激的母鼠一起哺乳可能会诱导参与情绪调节的神经递质系统发生持久变化。在这个模型中，使用神经化学和药理学方法进行进一步实验将很有意义。
