The activity of the hypothalamus–pituitary–adrenal (HPA) axis is pivotal in homeostasis and presides the adaptative response to stress. Dopamine Transporter (DAT) plays a key role in the regulation of the HPA axis. We used young adult female DAT Knockout (KO) rats to assess the effects of DAT ablation (partial, heterozygous DAT+/-, or total, homozygous DAT-/-) on vulnerability to stress. DAT-/- rats show profound dysregulation of pituitary homeostasis, in the presence of elevated peripheral corticosterone, before and after acute restraint stress. During stress, DAT-/- rats show abnormal autonomic response at either respiratory and cardiovascular level, and delayed body temperature increase. DAT+/- rats display minor changes of hypophyseal homeostatic mechanisms. These rats display a similar pituitary activation to that of the control animals, albeit in the presence of higher release of peripheral corticosterone than DAT-/- after stress, and reduced temperature during stress. Our data indicate that DAT regulates the HPA axis at both the central and peripheral level, including autonomic function during stress. In particular, the partial deletion of DAT results in increased vulnerability to stress in female rats, which display central and peripheral alterations that are reminiscent of PTSD, and they might provide new insights in the pathophysiology of this disorder.

中文翻译：

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缺乏多巴胺转运蛋白的大鼠表现出更高的脆弱性和对急性应激的异常自主反应。

下丘脑-垂体-肾上腺（HPA）轴的活动在体内平衡中起关键作用，并负责对压力的适应性反应。 多巴胺转运蛋白（DAT）在HPA轴的调节中起关键作用。我们使用了年轻的成年雌性DAT敲除（KO）大鼠来评估DAT消融（部分，纯合DAT +/-，或全部，纯合DAT-/-）对压力脆弱性的影响。DAT-/-大鼠在急性束缚应激前后都表现出严重的垂体稳态失调，外周皮质酮水平升高。在压力期间，DAT-/-大鼠在呼吸和心血管水平上均显示出异常的自主神经反应，并延迟了体温升高。DAT +/-大鼠显示垂体稳态机制的微小变化。这些大鼠表现出与对照动物类似的垂体激活，尽管在应激后外周皮质酮的释放高于DAT-/-，并且在应激期间温度降低。我们的数据表明，DAT在中央和周围水平都调节HPA轴，包括在压力下的自主功能。特别是，DAT的部分缺失会导致雌性大鼠对压力的脆弱性增加，而雌性大鼠的中枢和外周改变会让人联想到PTSD，并且可能为这种疾病的病理生理学提供新的见解。