COLLABORATIVE MOOD DISORDERS INITIATIVE

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。 该项目评估促肾上腺皮质激素释放因子1受体(CRF 1)拮抗剂在我们测量大鼠恐惧和焦虑中的效果，并将其与我们的条件性恐惧测量进行比较。我们发现，当大鼠脑室内给予CRF或长期暴露于强光(依赖于终纹床核(BNST))时，GSK CRF 1拮抗剂可阻断声休克幅度的增加，但当在先前与足击(依赖于杏仁中央核(CEA))配对的线索存在的情况下增加惊吓时，GSK CRF 1拮抗剂却不能阻止这种增加。 我们发现，通过病毒载体基因转移，CRF在杏仁核中央核的过度表达导致了几项指标的持续增加，这些指标表明焦虑持续增加。杏仁中央核外侧区的CRF神经元投射到终纹床核。含有降钙素基因相关肽(CGRP)的轴突投射到这些细胞，将CGRP局部注入CEA有助于惊厥，这一作用可被CRF1拮抗剂阻断。这项资助已经续期五年，在此期间，我们将继续关注CRF1拮抗剂在焦虑中的作用。

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. This project evaluates the effects of corticotropin releasing factor 1 receptor (CRF 1) antagonists in our measures of fear and anxiety in rats and compare it to our measure of conditioned fear. We found that the GSK CRF 1 antagonist blocks the increase in acoustic startle amplitude when rats are given CRF intraventricular or when they are exposed to bright light for long periods of time (dependent on the bed nucleus of the stria terminalis (BNST) but not when startle is increased in the presence of a cue previously paired with footshock (dependent on the central nucleus of the amygdala (CeA). We found that over-expression of CRF in the central nucleus of the amygdala using viral vector gene transfer led to a persistant increase in several measures that suggested a persistent increase in anxiety. CRF neurons in the lateral division of the central nucleus of the amygdala project to the bed nucleus of the stria terminalis. Axons containing calcitonin gene related peptide (CGRP) project to these cells and local infusion of CGRP into the CeA facilitate startle, an effect that is blocked by a CRF1 antagonist. This grant has been renewed for another five years during which time we will continue to look at the role of CRF1 antagonists in anxiety.