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 evaluate 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 but not when startle is increased in the presence of a cue previously paired with footshock. Because the first two measures of anxiety are dependent on a brain area called the bed nucleus of the stria terminalis, but the last measure is dependent on the amygdala, we believe that the CRF antagonist may work by blocking receptors in the bed nucleus of the stria terminalis. We found that over-expression of CRF in the central nucleus of the amygdala using viral vector gene transfer leads to a persistent increase in several measures that suggests a persistent increase in anxiety.
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