Male-female differences in rat hypothalamic-pituitary-adrenal axis responses to nicotine stimulation

Hypothalamic-pituitary-adrenal (HPA) axis responsiveness differs physiologi cally and pharmacologically between the sexes (sexual diergism). Central ni cotinic receptors modulate this endocrine axis. Previous studies have estab lished that nicotine (NIC) stimulates the HPA axis; however, only male anim als have been used. We have demonstrated that plasma arginine vasopressin ( AVP) and adrenocorticotropic hormone (ACTH) concentrations showed greater r esponsiveness in male than in female rats pretreated with scopolamine (SCOP ), a muscarinic antagonist, followed by physostigmine (PHYSO), an acetylcho linesterase inhibitor. These results suggest that the SCOP + PHYSO effects may have resulted from an indirect nicotinic effect caused by increased syn aptic acetylcholine with simultaneous muscarinic antagonism. In the present study, we investigated nicotinic cholinergic influences on HPA axis activi ty in male and female rats by administering NIC (0, 0.03, 0.1, 0,3, or 0.5 mg/kg) and determining plasma AVP, ACTH, and corticosterone (CORT) response s. Male rats had a significantly greater, dose-related AVP response to NIC than did females. In contrast, female rats had significantly greater, dose- related ACTH and CORT responses to NIC than did males. Hormone responses fo llowing NIC were similar to hormone responses following SCOP + PHYSO. These results suggest nicotinic receptors influence the HPA axis differentially in male and female rats. (C) 2001 Elsevier Science Inc.