Pituitary-adrenal responses to sub-chronic treatment with phenobarbital and/or phenytoin (diphenylhydantoin) in rats.
The response of the pituitary-adrenal axis of the male rat to sub-chronic dose treatment with phenobarbital and/or phenytoin under basal and stress conditions was investigated. Plasma corticosterone levels were measured in rats sacrificed either in the morning or in the afternoon, subjected or not to 2 hours of immobilization stress. Phenobarbital did not seem to significantly affect the pituitary-adrenal activity under basal conditions or in the response to stress. Phenytoin induced a disruption of the corticosterone diurnal variation present in the rat under basal conditions and seemed to partially inhibit the pituitary-adrenal response to stress when applied in the morning. The combined treatment with phenobarbital and phenytoin affected the afternoon rise in corticosterone levels present under basal conditions, as well as stress response at the same time of the day. The reported results agree with the hypothesis about the existence of mechanisms controlling ACTH release under basal conditions, dissociable from those controlling ACTH release in response to stress situations, and that phenytoin could influence some or others differently, depending on the animal's endocrine situation.
D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000523:psychology; D013997:Time Factors
D010672:Phenytoin; D003345:Corticosterone; D010634:Phenobarbital