Macrì Simone, Chiarotti Flavia, Würbel Hanno
Institute of Animal Sciences, Swiss Federal Institute of Technology (ETH), Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Behav Brain Res. 2008 Aug 22;191(2):227-34. doi: 10.1016/j.bbr.2008.03.031. Epub 2008 Apr 1.
Postnatal manipulations such as brief (early handling, EH) and long, daily mother-offspring separations (maternal separation, MS) in rats are used to study the mechanisms underlying developmental plasticity of stress and fear responses, and to model stress-related disorders in humans and in non-human animals. Current evidence suggests that, compared to non-handled rats, EH reduces hypothalamic-pituitary-adrenal (HPA) reactivity in the adult offspring through stimulating increased levels of active maternal care. In contrast, despite a similar increase in active maternal care, MS does not reduce HPA reactivity, thus suggesting that long mother-offspring separations may counteract the effects of increased active maternal care. We therefore attempted to selectively manipulate levels of active maternal care and durations of mother-offspring separations in neonate rats. Rat pups were exposed to different combinations of EH and MS from postnatal day (PND) 2 to 10 using a split-litter design. Maternal behaviour was recorded from PND 2 to 8 and behavioural and endocrine responses to stress were studied in adult male offspring. Low levels of maternal care combined with long mother-offspring separations increased HPA-reactivity compared to both high maternal care combined with long mother-offspring separations and low maternal care combined with brief separations. These findings further support the hypothesis that active maternal care and long mother-offspring separation act independently, and exert opposing effects, on adult offspring's HPA responses, but that increased maternal care may buffer the adverse consequences of long separations.
产后操作,如对大鼠进行短暂(早期处理,EH)和长期、每日的母婴分离(母体分离,MS),被用于研究应激和恐惧反应发育可塑性的潜在机制,并模拟人类和非人类动物中与应激相关的疾病。目前的证据表明,与未处理的大鼠相比,EH通过刺激增加积极的母性照料水平,降低成年后代下丘脑-垂体-肾上腺(HPA)反应性。相比之下,尽管积极的母性照料有类似增加,但MS并未降低HPA反应性,因此表明长期的母婴分离可能抵消积极母性照料增加的影响。因此,我们试图选择性地操纵新生大鼠积极母性照料的水平和母婴分离的时长。从出生后第2天(PND)到第10天,采用分窝设计,将幼鼠暴露于EH和MS的不同组合中。记录从PND 2到8的母性行为,并研究成年雄性后代对应激的行为和内分泌反应。与高母性照料与长期母婴分离以及低母性照料与短暂分离相比,低水平母性照料与长期母婴分离会增加HPA反应性。这些发现进一步支持了以下假设:积极的母性照料和长期的母婴分离对成年后代的HPA反应独立起作用,且产生相反的影响,但增加母性照料可能缓冲长期分离的不良后果。