Repeated exposure to a moderately intense stressor typically produces attenuation of the hypothalamic-pituitary-adrenal (HPA) axis response (habituation) on re-presentation of the same stressor; however, if a novel stressor is presented to the same animals, the HPA axis response may be augmented (sensitization). The extent to which this adaptation is also evident within neural activity patterns is unknown. This study tested whether repeated ferret odor (FO) exposure, a moderately intense psychological stressor for rats, leads to both same-stressor habituation and novel-stressor sensitization of the HPA axis response and neuronal activity as determined by immediate early gene induction (c-fos mRNA). Rats were presented with FO in their home cages for 30 min a day for up to 2 wk and subsequently challenged with FO or restraint. Rats displayed HPA axis activity habituation and widespread habituation of c-fos mRNA expression (in situ hybridization) throughout the brain in as few as three repeated presentations of FO. However, repeated FO exposure led to a more gradual development of sensitized HPA-axis and c-fos mRNA responses to restraint that were not fully evident until after 14 d of prior FO exposure. The sensitized response was evident in many of the same brain regions that displayed habituation, including primary sensory cortices and the prefrontal cortex. The shared spatial expression but distinct temporal development of habituation and sensitization neural response patterns suggests two independent processes with opposing influences across overlapping brain systems.

译文

反复暴露于中等强度的应激源通常会在重新呈现相同的应激源时导致下丘脑-垂体-肾上腺 (HPA) 轴反应 (习惯) 的减弱; 但是,如果向同一动物呈现一种新型的应激源,则可能会增强HPA轴反应 (敏化)。在神经活动模式中这种适应的程度也很明显是未知的。这项研究测试了反复暴露的雪貂气味 (FO) (一种中等强度的大鼠心理压力源) 是否会导致HPA轴反应和神经元活动的相同压力源习惯和新压力源敏化 (由立即的早期基因诱导确定) (c-fos mRNA)。每天在家养中给大鼠30分钟的FO,最多2周,然后用FO或约束对大鼠进行攻击。大鼠在整个大脑中显示出HPA轴活动的习惯性和c-fos mRNA表达的广泛习惯性 (原位杂交),其中只有三个重复的FO表现。然而,反复的FO暴露导致致敏的HPA轴和c-fos mRNA对约束的反应逐渐发展,直到先前的FO暴露14 d后才完全明显。在许多表现出习惯性的相同大脑区域 (包括初级感觉皮层和前额叶皮层) 中,敏化反应都很明显。习惯和敏化神经反应模式的共享空间表达但时间上的不同发展表明,两个独立的过程在重叠的大脑系统中具有相反的影响。

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