title: Dissociation of the effect of aminoglutethimide on corticosterone biosynthesis from ataxic and hypothermic effects in DBA and C57 mice.
abstract: 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.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, Portland, OR 97201.
authors.forename: A J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: E J
authors.initials: EJ
authors.lastname: Gallaher
authors.forename: L D
authors.initials: LD
authors.lastname: Keith
mesh_terms: D000315:Adrenalectomy; D000616:Aminoglutethimide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000097:blood / Q000209:etiology
chemical_list: D000616:Aminoglutethimide; D003345:Corticosterone