The physical context of previous stress exposure modifies hypothalamic–pituitary–adrenal responses to a subsequent homotypic stress

Abstract The hypothalamic–pituitary–adrenal (HPA) axis becomes less responsive to some types of repeated stress over time, a process termed habituation. Many facets of the stressful stimulus can modify such HPA responses to stressors, such as predictability and controllability. However, the physical context in which the stressor occurred may also provide a discriminative stimulus that can affect the HPA response to that stressor. In the present study, we examined whether a change in the context in which stress exposure occurs can alter HPA responses to a subsequent to that homotypic stressor. Three separate contexts were produced by manipulating odor cues. Rats housed in the 3 context rooms exhibited similar HPA responses to acute 30-min restraint or repeated (8th) 30-min restraint in their home environments. However, rats that were restrained for 30 min per day for 7 days in a room in one context and then restrained on day 8 in a novel context exhibited attenuated habituation compared to rats restrained on day 8 in the familiar context. These results provide evidence that repeated stress-induced HPA activity depends, in part, on the context in which the stress is experienced.