COLLABORATIVE MOOD DISORDERS INITIATIVE

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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.