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Submitted on June 6, 2003
Accepted on August 11, 2003
1 Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, OH 45267-0559; Bryan L. Bodie is deceased. This work is dedicated to his memory.
* To whom correspondence should be addressed. E-mail: james.herman{at}uc.edu.
Predator exposure is a naturalistic stressor of high ethological relevance. In the current study, our group examined central and peripheral integration of stress responses in rats following acute or repeated exposure to a natural predator (cat). Acute cat exposure rapidly induced HPA axis activation and paraventricular nucleus (PVN) CRH mRNA production. Repeated daily cat exposure (7 and 14 days) also upregulated PVN mRNA CRH expression, but did not result in frank adrenocortical hyperactivity. Unlike other chronic homotypic stress regimens, repeated cat exposure facilitated corticosterone secretion following the 6th or 13th day of exposure. Notably, ACTH secretion and central amygdaloid nucleus CRH mRNA expression were enhanced in animals that were pre-exposed to the holding chamber relative to chamber-naïve rats, suggesting that contextual cues can sensitize subsequent responses to a fearful stimulus. Analysis of c-fos activation was then used to identify brain circuits activated by acute predator stress. Cat exposure elicited a pattern of central c-fos activation that differed substantially from that following either restraint or hypoxia. Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical 'brain defense circuit' (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus and dorsal premammillary nucleus). Surprisingly, acute cat exposure did not induce c-fos expression in the PVN. In summary, the data indicate that 1) predation stress invokes a unique stress circuitry that promotes homotypic sensitization of the HPA axis, and 2) familiarization of animals to testing environments can prime central stress pathways to respond robustly to novel threats.
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