Responses of the HPA axis after chronic variable stress: effects of novel and familiar stressors.

OBJECTIVES: We examined the role that novelty plays in determining interactions between chronic and acute stress, when both the chronic and acute stressors emphasize emotional processing (i.e. stressful stimuli that do not present immediate threats to somatic homeostasis, and are processed primarily by limbic and forebrain circuits).

METHODS: Rats were exposed to a chronic variable stress (CVS) regimen, and were subsequently tested to evaluate responses to novel and familiar acute stressors. One group was exposed to CVS that included restraint, and was then tested with this familiar stressor. Another group was exposed to CVS that did not include restraint, and were tested with restraint as a novel stressor. Additional rats were not chronically stressed. Plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) were assayed.

RESULTS: When the rats were exposed to familiar acute stress after CVS, ACTH responses were blunted. The ACTH responses were normal in the rats that were tested with novel acute stress--the responses resembled those of rats that had no prior stress experience. CORT responses did not differ between the groups, regardless of stress history.

CONCLUSIONS: Despite the fact that all the chronic and acute stressors emphasized emotional processing of aversive stimuli, and thus likely involved overlapping limbic and forebrain circuits, the hormonal responses differed depending upon familiarity with the acute stressor. Further research is required to identify the neuronal mechanisms that mediate these differing responses to novel and familiar emotional stressors.

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