DISSOCIATION OF THE EFFECT OF AMINOGLUTETHIMIDE ON CORTICOSTERONE BIOSYNTHESIS FROM ATAXIC AND HYPOTHERMIC EFFECTS IN DBA AND C57 MICE

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 pr oduces many negative side effects such as hypotension and hypoglycemia . Aminoglutethimide is a steroid synthesis inhibitor which depletes ad renocortical hormones without these negative effects. However, aminogl utethimide itself has been shown to produce behavioral and physiologic al deficits. In the present experiments, dose-response relationships w ere determined for the effects of aminoglutethimide on corticosterone levels, motor coordination, and body temperature in C57 and DBA mice. Aminoglutethimide (5.4-54mg/kg) inhibited the increase ill plasma cort icosterone concentrations normally observed in response to restraint s tress. Only at higher doses (170-1,000 mg/kg) were rotarod performance and body temperature affected. The corticosterone response to restrai nt stress recovered fully between 12 and 24 h after aminoglutethimide. In the present study, doses of aminoglutethimide were found that temp orarily inhibit stressed corticosterone release without producing moto r deficits and temperature decreases. These results indicate that amin oglutethimide is a potential substitute for adrenalectomy in studies o n the effects of removal of adrenocortical hormones.