Touyarot K, Venero C, Sandi C
Department of Psychobiology, Universidad Nacional de Educacion a Distancia, Ciudad Universitaria s/n, 28040 Madrid, Spain.
Psychoneuroendocrinology. 2004 Feb;29(2):290-305. doi: 10.1016/s0306-4530(03)00031-3.
Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find a neurobiological substrate that specifically correlated with the differential cognitive vulnerability to chronic stress shown by animals with a different novelty reactivity, this study confirms the hypothesis that rats differ in their susceptibility to display stress-induced impairments in hippocampus-dependent spatial learning tasks. In addition, it provides a model to further search for the neurobiological substrate(s) involved in the differential susceptibility to develop stress-induced cognitive impairments.
尽管已有报道称慢性应激会对海马体的结构和功能产生有害影响，但研究推测，个体在易受应激诱导的认知改变影响方面可能存在差异。本研究旨在评估：（i）对新奇事物的行为反应中的个体差异是否与成年幼鼠在慢性应激后出现空间学习缺陷的不同易感性有关；（ii）应激诱导的认知改变中的个体差异在多大程度上可能与特定神经生物学底物的改变有关。将4个月大的雄性Wistar大鼠根据其对新环境的运动反应分为低反应性（LR）或高反应性（HR），然后让它们要么接受21天的心理社会应激（包括每只成年幼鼠每天与一只新的中年大鼠共同居住），要么不做处理。结果显示，心理社会应激在HR大鼠而非LR大鼠中导致水迷宫空间学习出现明显缺陷。接着，第二个实验研究了在基础条件下以及暴露于慢性社会应激后，HR和LR大鼠海马体中糖皮质激素受体（MR和GR）以及细胞黏附分子（NCAM和L1）的可能差异表达。尽管慢性应激导致MRs和NCAM - 140亚型的海马体表达减少，但在有和没有空间学习障碍的应激大鼠中，即分别在HR应激大鼠和LR应激大鼠中，这些分子的水平并无差异。然而，应该注意的是，心理社会应激诱导的NCAM - 140海马体表达减少在HR应激大鼠中尤为明显。然而，GRs、NCAM - 120和NCAM - 180亚型以及L1的表达不受应激影响，无论动物的反应性如何。因此，尽管我们未能找到与具有不同新奇反应性的动物对慢性应激的不同认知易感性具体相关的神经生物学底物，但本研究证实了以下假设：大鼠在显示应激诱导的海马体依赖性空间学习任务损伤的易感性方面存在差异。此外，它提供了一个模型，以进一步寻找参与对应激诱导的认知损伤不同易感性的神经生物学底物。
