EARLY LIFE STRESS IN NON HUMAN PRIMATES AND HUMANS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项工作的目标是开发一种客观的方法来测量恒河猴和人类的恐惧抑制。 在大鼠中，我们已经开发了这样一个程序，其中一对线索（AX+）与厌恶的气流配对，另一对线索（BX-）不与厌恶的气流配对。 在这些条件下，老鼠学会了害怕A，而不是害怕B，害怕X是在中间的某个地方。 重要的是，当我们在B在场的情况下测试A对B的恐惧时，我们看到B抑制了A对B的恐惧。 我们现在已经在人类身上建立了AX+，BX-的辨别能力，并正在创伤后应激障碍患者身上进行测试。 此外，我们已经在耶基斯的恒河猴中建立了AX+，BX-，现在正在发育期间与母亲短暂分离的猴子中进行测试。 最后，我们一直在测试各种抗焦虑化合物如何影响猴子的恐惧强化惊吓。 我们发现吗啡和地西泮，而不是丁螺环酮，剂量依赖性地阻断恐惧增强惊吓，表明我们的测试能够检测出抗焦虑的化合物。

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.