EFFECT OF ADRENALECTOMY AND REPLACEMENT WITH ADRENOCORTICAL STEROIDS ON BARBITAL ANESTHESIA IN MICE

¹ Department of Pharmacology and Endocrinological Laboratories, School of Medicine, Gunma University, Maebashi, Japan

The effects of adrenalectomy and of replacement with corticoids on the onset and the duration or barbital anesthesia and on the concentration of the drug in the brain at various times after the injection were ascertained.

Adrenalectomy reduced the induction time of barbital anesthesia by about 50 per cent. Pretreatment of adrenalectomized mice with cortisone acetate and hydrocortisone acetate restored the onset to normal, while DCA and saline had no effect. Adrenalectomized mice untreated or treated with saline died or remained anesthetized for 24 hours after injection of barbital. Pretreatment with cortisone acetate and hydrocortisone acetate completely protected against anesthetic death. The former returned the anesthesia time to normal level, but the latter decreased it significantly. DCA protected adrenalectomized mice against anesthetic death, but the anesthesia time remained greatly prolonged. For the first 20 minutes after injection, the concentration of barbital in the brain of adrenalectomized mice increased at the same rate as in intact animals, but increased beyond the maximal value of the latter at 30 to 60 minutes after the injection. Pretreatment of adrenalectomized animals with cortisone or hydrocortisone reduced the rate of uptake of barbital by the brain to normal levels. For the subsequent 2 hours, the rate of discharge of barbital from the brain was more rapid in the pretreated animals than in intact controls. DCA had no effect upon the rate of uptake or discharge in adrenalectomized mice. The effect of the corticoids upon the course of anesthesia is considered to be related to their effects upon barbital concentrations in the brain.

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