Delayed Feedback Inhibition of Stress-Induced Activation of Pituitary-Adrenal Function: Effects of Varying Dose, Rate and Duration of Corticosterone Administration and of Telencephalon Removal

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Abstract
The effects of varying dose, rate and duration of corticosterone (cpd B) administration on the inhibition of the pituitary-adrenal response to stress by delayed feedback and whether brain structures located in the telencephalon are essential for this feedback action were determined. In the 1st experiment, 10 min infusions of cpd B i.p. at rates of 14, 32 or 40 .mu.g/min produced elevations in plasma cpd B which were physiological in time course and amplitude. To study the effects of such infusions on pituitary-adrenal responses to stress, other rats were exposed to ether for 2 min at various times after completion of infusion; blood samples were collected 15 min after stress. With the 14 .mu.g/min infusion, stress applied at 25, 60 or 120 min after the termination of infusion produced increases (P < 0.05) in plasma cpd B levels, so there was no indication of feedback inhibition. Infusion of 32 .mu.g/min for 10 min inhibited the stress response at 120 but not 25 or 60 min. Infusing 40 .mu.g of cpd B/min for 10 min blocked responses at 25, 60 and 120 min; because of the inhibition of the stress response at 25 min, a 1-2 h silent period preceding delayed feedback does not appear obligatory. Delayed feedback apparently is level-sensitive and proportional in action. In the 2nd experiment, duration and rate of cpd B administration were varied. The rats received 140 .mu.g cpd B i.p. as a bolus or infused over 20, 40 or 60 min. The bolus injection and 20 min infusion produced rapid and relatively high peaks in plasma cpd B levels, but responses to ether stress applied at 45 or 105 min were not blocked. Infusing 140 .mu.g over 40 min blocked the stress response at 105 but not 45 or 15 min after termination of infusion. The 60 min infusion inhibited responses to stress at 105 and 45 but not 15 min. Delayed feedback may not be rate-sensitive, and duration of feedback signal is an important variable. The final experiment demonstrated that delayed feedback persists 24 h after removal of the telencephalon. Limbic and other structures of the telencephalon are not essential for the inhibition of ether stress-induced activation of the pituitary-adrenal system by delayed feedback.