Effects of Corticosterone, Dexamethasone and Surgical Isolation of the Medial Basal Hypothalamus on Rapid Feedback Control of Stress-Induced Corticotropin Secretion in Female Rats¹

Abstract

These studies were designed to determine whether physiological transients in plasma corticosterone levels exert a rapid or rate-sensitive feedback inhibition of the pituitary-adrenal response to ether stress, to compare effects of corticosterone and dexamethasone (Dex) on such control and to determine whether brain structures located outside of the medial basal hypothalamus (MBH) are essential for rapid feedback. Ten-minute infusions of corticosterone ip into pentobarbital-anesthetized rats at rates of 4 or 8 μg/min produced elevations in plasma corticosterone levels which were physiological in time course and amplitude. To study the effect of such infusions on adrenocortical responses to stress, rats were exposed to ether for 2 min during or at various times after infusion; blood samples were obtained 15 min after stress. Whereas infusion of vehicle was compatible with corticosterone responses to stress at all times tested, corticosterone infused at 4 μg/min blocked the response to ether if this stress was presented at 5 but not at 20 or 35 min after the start of infusion. Infusion of corticosterone at 8 μg/min blocked responses at 5 and 20 but not at 35, 70 and 130 min. Blockade of stress responses was associated with the rising phase of the steroid transients and not with absolute corticosterone levels. In contrast, 10-min infusion of Dex at rates of 1, 5 or 10 μg/min did not block responses to ether applied at 5, 20 or 30 min. However, the highest dose partially suppressed responses at 130 min. In similar studies performed at 2–5 weeks after complete surgical isolation of MBH, 10-min infusion of corticosterone at 8 μg/min blocked the corticosterone response to ether applied at 5 min after the start of infusion. These findings indicate that physiological transients in circulating corticosterone levels can rapidly inhibit the pituitary-adrenal response to ether stress and suggest that Dex is ineffective in this regard. The persistence of rapid feedback following surgical isolation of MBH suggests that this regulation is exerted via structures residing within the MBHpituitary unit.