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。 这项工作的目标是开发一种客观的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。我们现在已经在人类中建立了AX+，BX-歧视，并正在创伤后应激障碍患者中进行测试。此外，我们已经在耶克斯的恒河猴体内建立了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。最后，我们一直在测试不同的抗焦虑化合物如何影响猴子的恐惧和惊吓。我们已经发现，吗啡和安定，而不是丁螺环酮，可以剂量依赖地阻断恐惧增强的惊吓，这表明我们的测试能够检测到人体内具有抗焦虑作用的化合物。

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 goal of this work is to develop an objective 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 now set up the AX+, BX- discrimination in humans and are testing it in patients with post-traumatic stress disorder. In addition, we have 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. Finally, we have been testing how various anxiolytic compounds affect fear potentiated startle in monkeys. We have found that morphine and diazepam, but not buspirone, dose-dependently block fear potentiated startle, indicating our test is capable of picking up compounds that are anxiolytic in people.