Article ID Journal Published Year Pages File Type
4319247 Brain Research Bulletin 2011 8 Pages PDF
Abstract

Hypothalamic–pituitary–adrenal (HPA) responses to single-dose nicotine (NIC) are sexually diergic: Female rats have higher adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than do males. In the present study we determined HPA responses in male and female rats following single doses of NIC, a single-dose of NIC immediately following continuous NIC for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) following continuous NIC infusion for two weeks. Blood sampling occurred before and after MEC and NIC administrations for the determination of ACTH and CORT.In accordance with our previous findings, female ACTH and CORT responses to single-dose NIC were greater than male responses. This sex difference remained after single-dose NIC followed continuous NIC infusion, but HPA responses in both sexes were significantly lower in magnitude and duration than in the single-dose NIC alone groups. Sex differences also were observed following NIC withdrawal by MEC: the HPA responses to pretreatment with MEC were significantly higher in magnitude and duration in the continuous NIC groups than in the single-dose NIC groups. These results demonstrate that HPA responses to NIC are reduced and transient following continuous NIC infusion but are enhanced and sustained following NIC withdrawal by MEC after continuous NIC, suggesting that NIC habituation and withdrawal influence the stress responses in a diergic manner. These findings highlight the importance of sex differences in the effect of NIC on HPA axis activity and stress responsiveness, which may have implications for directing NIC-addiction treatment specifically towards men and women.

► ACTH and CORT responses to single-dose NIC were sexually diergic: females > males. ► Sexually diergic ACTH and CORT responses were lower after continuous NIC. ► Sexually diergic ACTH and CORT responses were higher following NIC withdrawal by MEC. ► Our work emphasizes diergic effects of NIC habituation and withdrawal on the HPA axis.

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