Stressor-selective role of the ventral subiculum in regulation of neuroendocrine stress responses

The ventral subiculum (vSUB) confers inhibitory effects of the hippocampus on hypothalamo-pituitary-adrenocortical (HPA) axis responses to novelty and restraint. The current study was designed to evaluate the role of the vSUB in regulating HPA axis responses to stressors of diverse modalities. Male Sprague Dawley rats received bilateral ibotenic acid or saline injections into the region of the vSUB. Corticosterone secretion was assessed after exposure to hypoxia and elevated plus maze, with the two stress exposures occurring 5 d apart. Peak corticosterone responses to hypoxia were reduced in vSUB-lesion animals, indicating an attenuation of HPA axis responsiveness. A subsequent study revealed that hyporesponsivity to hypoxia was evident in chamber-naive as well as chamber-adapted animals, verifying that this effect was independent of previous experience in the testing environment. In contrast, the effects of vSUB lesions on corticosterone responses to the elevated plus maze exposure were substantially more circumspect, being limited to a slight increase in secretion at the 2-h poststress time point. The limited vSUB lesion-induced increase in the plasma corticosterone response to elevated plus maze exposure occurred despite an increased open-arm time in the maze, suggesting that lesions reduced anxiety-like behavior. In combination with previous studies, these data suggest that the vSUB has excitatory as well as inhibitory input into HPA axis responsivity, depending on the nature of the stressful stimulus, and suggest that behavioral and neuroendocrine responses to stressful or anxiogenic stimuli may be dissociable.