| Abstrakt: |
Adrenocorticotrophic hormone (ACTH) and corticosterone responses to cholinergic stimulation are greater in male rats and mice than in females. To explore the role of M2 muscarinic receptors in this sex difference, we administered the nonselective muscarinic agonist, oxotremorine, the acetylcholinesterase inhibitor, physostigmine, and saline (a mild stressor) to male and female M2 receptor knockout (KO) and wild-type (WT) mice of the same genetic background. Because M2 receptors function primarily as presynaptic autoreceptors, we hypothesized that their absence in M2 KO mice would increase the sensitivity of hormone responses to cholinergic stimulation in these groups. Both male and female M2 KO mice were significantly more responsive to the stress of saline injection than were their WT counterparts. Oxotremorine and physostigmine increased ACTH and corticosterone in all four groups, but to a significantly greater degree in KO males compared to WT males, KO females, and WT females. The increase in ACTH also was significantly greater in WT males compared to WT females. By contrast, the increase in corticosterone was significantly more in females compared to males, independent of genotype. Following pretreatment with the nonselective muscarinic antagonist, scopolamine, ACTH and corticosterone responses to oxotremorine and to saline in the M2 KO mice were comparable with those of their WT counterparts. These findings suggest that the M2 muscarinic receptor subtype influences male and female pituitary-adrenal responses following stimulation by both mild stress and cholinergic drugs. The M2 receptor appears to regulate ACTH responses to cholinergic stimulation in males but not in females; however, other muscarinic receptors may be involved because corticosterone responses were higher in females compared to males. Because ACTH and corticosterone responses were greater in male and female M2 KO mice, the M2 receptor appears to dampen the stress response. [ABSTRACT FROM AUTHOR] |
