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早期以抚摸形式进行的行为丰富化会使幼鼠对抗焦虑药物无反应,并提高海马体中的神经生长因子水平。

Early behavioural enrichment in the form of handling renders mouse pups unresponsive to anxiolytic drugs and increases NGF levels in the hippocampus.

作者信息

Cirulli Francesca, Capone Francesca, Bonsignore Luca T, Aloe Luigi, Alleva Enrico

机构信息

Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.

出版信息

Behav Brain Res. 2007 Mar 28;178(2):208-15. doi: 10.1016/j.bbr.2006.12.018. Epub 2006 Dec 21.

DOI:10.1016/j.bbr.2006.12.018
PMID:17223206
Abstract

Early life experiences, such as early handling, can influence neural development of rodents leading to changes in physiological and behavioural reactivity to stress. These effects are likely to be mediated by changes in maternal behaviour. This study analyzed the effects of different manipulations of the rearing environment on maternal behaviour and the behavioural and physiological response to mild challenges in CD-1 mouse pups early during development. Litters underwent either 15 min of neonatal handling (H) or were exposed briefly to an unfamiliar male intruder from postnatal (PND) days 2 to 14 (MI). Both groups were compared with litters which were not manipulated (NH). Compared to NH subjects, licking behaviour in the MI group was increased only on the first day of introduction of the male intruder, while the H group showed an increase in maternal behaviour on PND 10. On PND 8, pups ultrasonic vocalizations were recorded upon treatment with an anxiolytic drug (chlordiazepoxide 0, 2, or 7.5mg/kg). Results indicate that, although there were no differences among the groups when mice were injected with vehicle, handled subjects did not reduce their calling rate following drug administration, in contrast to the NH and MI groups. Following maternal separation and novelty exposure on PND 9, levels of hippocampal NGF increased significantly only in the H group. These data suggest that active pup manipulations in the form of handling favour behavioural and neural plasticity resulting in the maintenance of a high level of arousal and in increased neurotrophin levels in response to an acute manipulation. Changes in hippocampal levels of NGF might be involved in the appraisal of subtle changes in the early social environment.

摘要

早期生活经历,如早期触摸,会影响啮齿动物的神经发育,导致其对应激的生理和行为反应发生变化。这些影响可能是由母性行为的改变介导的。本研究分析了发育早期对CD-1小鼠幼崽饲养环境进行不同操作对母性行为以及对轻度挑战的行为和生理反应的影响。一窝幼崽接受了15分钟的新生期触摸(H组),或者从出生后(PND)第2天到第14天短暂暴露于陌生雄性入侵者(MI组)。将这两组与未进行操作的一窝幼崽(NH组)进行比较。与NH组相比,MI组的舔舐行为仅在引入雄性入侵者的第一天增加,而H组在PND 10时母性行为增加。在PND 8时,用一种抗焦虑药物(氯氮卓0、2或7.5mg/kg)处理幼崽后记录其超声波发声。结果表明,虽然在注射赋形剂时各组之间没有差异,但与NH组和MI组相比,接受触摸的幼崽在给药后并未降低其鸣叫率。在PND 9进行母鼠分离和新奇刺激后,仅H组海马神经生长因子(NGF)水平显著升高。这些数据表明,以触摸形式进行的主动幼崽操作有利于行为和神经可塑性,从而在急性操作时维持高水平的觉醒并提高神经营养因子水平。海马NGF水平的变化可能参与对早期社会环境细微变化的评估。

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