Dissociation of the effect of aminoglutethimide on corticosterone biosynthesis from ataxic and hypothermic effects in DBA and C57 mice

• Published in: Neuroendocrinology Vol. 58; no. 3; p. 303
• Main Authors: Roberts, A J, Gallaher, E J, Keith, L D
• Format: Journal Article
• Language: English
• Published: Switzerland 01-09-1993
• Subjects: Adrenalectomy; Aminoglutethimide - administration & dosage; Aminoglutethimide - pharmacology; Animals; Body Temperature - drug effects; Corticosterone - antagonists & inhibitors; Corticosterone - biosynthesis; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Motor Activity - drug effects; Restraint, Physical; Stress, Physiological - blood; Stress, Physiological - etiology
• ISSN: 0028-3835
• DOI: 10.1159/000126554

Adrenalectomy is frequently used to deplete adrenocortical hormones in physiological and receptor-binding studies in animals. However, this procedure is irreversible, removes both the cortex and medulla, and produces many negative side effects such as hypotension and hypoglycemia. Aminoglutethimide is a steroid synthesis inhibitor which depletes adrenocortical hormones without these negative effects. However, aminoglutethimide itself has been shown to produce behavioral and physiological deficits. In the present experiments, dose-response relationships were determined for the effects of aminoglutethimide on corticosterone levels, motor coordination, and body temperature in C57 and DBA mice. Aminoglutethimide (5.4-54 mg/kg) inhibited the increase in plasma corticosterone concentrations normally observed in response to restraint stress. Only at higher doses (170-1,000 mg/kg) were rotarod performance and body temperature affected. The corticosterone response to restraint stress recovered fully between 12 and 24 h after aminoglutethimide. In the present study, doses of aminoglutethimide were found that temporarily inhibit stressed corticosterone release without producing motor deficits and temperature decreases. These results indicate that aminoglutethimide is a potential substitute for adrenalectomy in studies on the effects of removal of adrenocortical hormones.