Sex differences in the long-lasting effects of a single exposure to immobilization stress in rats

• Females have higher basal ACTH and corticosterone levels than males.
• Females show similar ACTH but higher corticosterone response to stress than males.
• Females do not show immobilization-induced increases in basal hormone levels.
• Immobilization-induced hypoactivity is similar in the two sexes.
• Homotypic reduction of the response after prior immobilization is greater in females.

In male rats, a single exposure to a severe stressor such as immobilization (IMO) results in marked activation of the HPA axis and reduction of body weight gain. In addition, the HPA response to the same (homotypic) stressor is reduced, whereas the response to a different (heterotypic) stressor is enhanced for days. Although sex differences in the responsiveness of the HPA axis have been described, there are few studies about the influence of sex on long-lasting effects of stress. Thus, we have compared the consequences of a single exposure to IMO in male and female rats. Females showed a similar ACTH response to the first IMO associated with higher corticosterone, but they were more resistant than males to stress-induced loss of body weight. Unstressed females showed higher resting levels of ACTH and corticosterone, but they did not show the increase in the resting levels of HPA hormones observed in males on the day after IMO. During exposure to a different stressor (open-field) two days after IMO, enhanced corticosterone response and hypoactivity was observed in males, but not in females. Finally, a second exposure to IMO 8 days after the first one resulted in a reduction of the HPA response and of the negative impact on body weight as compared to the first exposure, and this protective effect was greater in females. In sum, IMO-exposed females showed a greater reduction of the response to a second IMO and appear to be more resistant than males to some of the negative impacts of IMO.