ENHANCED HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS RESPONSES TO PHYSOSTIGMINE IN NORMAL AGING

Background. The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physost igmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity. Methods . Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10- minute infusion of physostigmine (.0125 mg/kg) were compared between g roups of 10 normal older subjects(71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentr ations were measured to assess the comparability of the pharmacologic stimulus between groups. Results. Endocrine responses were substantial ly greater in older subjects than young subjects for ACTH (p < .01), b eta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentra tions did not differ between older and young subjects. Conclusion. Thi s study demonstrated increased HPA axis responsivity to a CNS choliner gic stimulus in normal human aging.