Development of tolerance to the stimulatory effect of neuroleptic butyrophenones on pituitary-adrenal activity in rats.
The effects of repeated administration of haloperidol (HAL) and clofluperol (CLO) on the responsiveness of pituitary-adrenal system to these drugs were studied in rats. Chronic treatment of animals with a daily i.p. dose of 5 mumol/kg of the drugs resulted in markedly attenuated responses of plasma corticosterone (CS) to challenge of the same dose of the same drug as compared to the acute treatment which caused a large increase in the plasma CS levels. Animals receiving a chronic HAL treatment showed a complete cross-tolerance to the stimulatory effect of CLO and a nearly complete cross-tolerance to that of chlorpromazine. The adrenal cortices of animals tolerant to HAL responded normally to exogenous ACTH. This result indicates that the tolerance to the stimulatory action of the butyrophenones may occur in the hypothalamo-pituitary axis.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004361:Drug Tolerance; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013997:Time Factors; D014272:Trifluperidol / Q000031:analogs & derivatives / Q000494:pharmacology
D014150:Antipsychotic Agents; D006220:Haloperidol; C023813:clofluperol; D014272:Trifluperidol; D003345:Corticosterone