Sexually diergic hypothalamic‐pituitary‐adrenal axis responses to single‐dose nicotine alone and following continuous administration of nicotine by osmotic mini‐pumps in rats

Abstract

Central cholinergic systems differentially modulate hypothalamic-pituitary-adrenal (HPA) axis activity in male and female animals (sexual diergism). Previous studies in our laboratory have demonstrated that HPA responses to nicotine (NIC) are sexually diergic, males having lower adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses to NIC than their female counterparts. The current study extends previous findings by determining the effects of a single-dose of NIC, and the effects of a single-dose of NIC immediately following continuous administration of NIC for 2 weeks, in male and female rats. Blood sampling occurred before and after NIC (0.3 mg/kg) or saline administration. Continuous administration of NIC was achieved by surgical implantation of Alzet® osmotic mini-pumps. As before, ACTH and CORT were measured. Male-female hormone responses to single-dose NIC support previous findings. Male-female differences to single-dose NIC remained following continuous administration of NIC; however, hormone responses to single-dose NIC in these groups were significantly lower. These results suggest that sexually diergic HPA responses to NIC are reduced following continuous NIC administration. The present study may have implications for further studies determining the association among stress, habituation of the HPA axis to chronic NIC use, and NIC withdrawal. Supported by 2004 PA Dept of Health Tobacco Settlement Funds to MER and by NIH grant MH28380 to RTR.