Patterns of Fos-Immunoreactivity in the CNS Induced by Repeated Hemorrhage in Conscious Rats: Correlations with Pituitary-Adrenal Axis Activity

While the present understanding of pituitary-adrenal function predicts attenuation of responses to a repeated stressor, experimental observations often show occurrence of potentiation rather than inhibition. The role of the CNS in this phenomenon was investigated in rats sustaining either a single (S-HEM) or a double episode (R-HEM) of hemorrhage. For S-HEM, blood was withdrawn over 3min and retransfused at 10min; for R-HEM, the stimulus was repeated at 90 min. S-HEM elicited 26- and 9-fold increases in circulating adrenocorticotropin (ACTH) and corticosterone, respectively. After R-HEM the plasma ACTH response was potentiated by 82%. Sixty min after S-HEM, Fos-like immunoreactivity (Fos-IR) was increased in medullary (solitary nucleus, NTS and ventrolateral medulla, VLM), pontine (locus coeruleus, LC and parabrachial nucleus, PBN), limbic (central amygdala, CNA and bed nucleus, BNST), and hypothalamic (supraoptic nucleus, SON and paraventricular nucleus, PVN) regions activated by hemodynamic stimuli. However after R-HEM, the Fos-IR response was significantly potentiated only in the VLM and PVN, while only a moderate increase was evident in the NTS. In other brain regions (LC, PBN, CNA, BNST, HPC and SON), Fos-IR either did not change or the increases were less than those observed after S-HEM. It is suggested that this plasticity in the pattern of neuronal activation following repetition of a stimulus may account for the maintenance of pituitary-adrenal secretory responses and its potentiation after R-HEM.