EARLY LIFE STRESS IN NON HUMAN PRIMATES AND HUMANS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是开发一种方法来衡量恒河猴和人类对恐惧的抑制。在大鼠中，我们已经开发出这样一种程序，其中一对线索(AX+)与厌恶气爆配对，而另一对线索(BX-)不与厌恶气爆配对。在这种情况下，老鼠学会了害怕A，而不是害怕B，而对X的恐惧介于两者之间。重要的是，当我们在B的存在下测试对A的恐惧时，我们发现B抑制了对A的恐惧。我们已经在人类中建立了AX+，BX-歧视，并在创伤后应激障碍患者中进行了测试。我们发现，PTSD患者没有表现出正常的条件性抑制，这意味着我们对PTSD的核心症状之一--即缺乏安全感--有了一个客观的衡量标准。 此外，我们在耶克斯的恒河猴身上建立了AX+，BX-，现在正在发育过程中与母亲短暂分离的猴子身上进行测试，以及在大脑不同区域受损的猴子身上进行测试。我们发现，恒河猴杏仁核的损伤阻止了习得，但与大鼠相比，恐惧的表达增强了惊吓，这应该是两者的阻断。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this study is to develop a way to measure inhibition of fear in rhesus monkeys and humans. In rats we have developed such a procedure in which one pair of cues (AX+) is paired with an aversive airblast and another pair of cues (BX-) is not paired with an aversive airblast. Under these conditions, rats learn to be afraid of A, not to be afraid of B and fear of X is some where in the middle. Importantly, when we test fear to A in the presence of B we see that B inhibits fear to A. We have set up the AX+, BX- discrimination in humans and are testing it in patients with post-traumatic stress disorder. We found that patients with PTSD do not show normal conditioned inhibition which means we have an objective measure of one of the core symptoms of PTSD, namely the inability to feel safe. In addition, we set up the AX+, BX- in rhesus monkeys at Yerkes and are now testing it in monkeys who have had separation from their mothers for brief periods of time during development as well as in monkeys that have had lesions of various brain areas. We found that lesions of the amygdala in rhesus monkeys block acquisition but expression of fear-potentiated startle, in contrast to rats, that should a blockade of both.