PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat

The mechanism(s) underlying hypoglycemia-associated autonomic failure (HAAF ) are unknown. To test the hypothesis that the activation of brain regions involved in the counterregulatory response to hypoglycemia is blunted with HAAF, rats were studied in a 2-day protocol. Neuroendocrine responses and b rain activation (c-Fos immunoreactivity) were measured during day 2 insulin -induced hypoglycemia (0.5 U insulin . 100 g body wt(-1) . h(-1) iv for 2 h ) after day 1 hypoglycemia (Hypo-Hypo) or vehicle. Hypo-Hypo animals demons trated HAAF with blunted epinephrine, glucagon, and corticosterone (Cort) r esponses and decreased activation of the medial hypothalamus [the paraventr icular (PVN), dorsomedial (DMH), and arcuate (Arc) nuclei]. To evaluate whe ther increases in day 1 Cort were responsible for the decreased hypothalami c activation, Cort was infused intracerebroventricularly (72 mug) on day 1 and the response to day 2 hypoglycemia was measured. Intracerebroventricula r Cort infusion failed to alter the neuroendocrine response to day 2 hypogl ycemia, despite elevating both central nervous system and peripheral Cort l evels. However, day 1 Cort blunted responses in two of the same hypothalami c regions as Hypo-Hypo (the DMH and Arc) but not in the PVN. These results suggest that decreased activation of the PVN may be important in the develo pment of HAAF and that antecedent exposure to elevated levels of Cort is no t always sufficient to produce HAAF.