Sexual diergism in rat hypothalamic-pituitary-adrenal axis responses to cholinergic stimulation and antagonism

The hypothalamic-pituitary-adrenal (HPA) axis has differential physiological activity in male and female animals (sexual diergism). Central cholinergic systems stimulate this endocrine axis. In the present study we investigated muscarinic and nicotinic cholinergic influences on HPA axis activity in male and female rats by pretreatment with selective cholinergic receptor antagonists followed by stimulation with physostigmine (PHYSO), an acetylcholinesterase inhibitor. Hormonal measures were plasma arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Male rats had significantly greater AVP and ACTH responses to PHYSO alone than did females. Scopolamine (SCOP) enhanced the AVP response to PHYSO to a greater extent in males than in females. In contrast, mecamylamine (MEC) enhanced the AVP response in females but decreased it in males. SCOP potentiated, and MEC inhibited, the stimulatory effect of PHYSO on ACTH in both sexes, but SCOP potentiation was greater in males, and MEC inhibition was greater in females. Absolute CORT increases following PHYSO were greater in females, but percent increases over baseline were greater in males. Similar to their effects on ACTH responses, MEC attenuated, and SCOP enhanced, CORT responses to PHYSO. These results suggest that cholinergic receptor subtypes may influence HPA axis activity differentially in male and female rats.