STRESS ALLOSTASIS: CRF, SEROTONIN AND THE BNST

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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. In 2009 we continued to examine the role of the BNST in stress related anxiety disorders, and it's modulation by serotonin (5-HT). We have shown that repeated restraint stress (RRS) induces a significant disruption of 5-HT receptor mRNA transcripts in the BNST. Significantly, the disruption of 5-HT receptor mRNA correlates with the expression of enhanced anxiety-like behavior in vivo. We have extended this work to show that a similar response is observed following repeated unpredictable shock stress (USS) and, hence, the genetic disruption appears to generalize to chronic traumatic stress. Importantly, the USS paradigm closely resembles the daily experience of many military personnel in combat zones, and we believe that USS may accurately model the conditions that can induce PTSD in a subpopulation of combatants. Our prediction is that repeated traumatic stress results in a sensitization of CRF containing neurons in the BNST, which ultimately results in a pathological state of hyperarousal. We have developed a transgenic mouse that expresses a green fluorescent protein only in CRF neurons, and we are using this novel model to examine the effects of RSS and USS on the physiological properties of CRF containing neurons in the BNST.