Amitriptyline: sex-dependent effect on sympathetic response and anxiety in rats submitted to early maternal separation and variable chronic stress in adulthood

The aim of the present study was to determine the effects of chronic treatment with the antidepressant amitriptyline on sympathetic nervous system activity and anxiety in male and female rats submitted to maternal separation (MS) and variable chronic stress (VCS). We observed that the treatment with amitriptyline produced a significant increase in norepinephrine (NE) plasma levels in non-maternally separated (NMS), non-stressed (NVCS) males in relation to vehicle-treated males, whereas in females the antidepressant produced a significant decrease in epinephrine (E) and NE when compared to the vehicle-treated group. In NMS/VCS males, amitriptyline produced a significant increase in the time spent on the open arms (TIME) in relation to the vehicle-treated group. In NMS/VCS females, amitriptyline produced a significant increase in TIME when compared to males. MS/VCS females showed a significant increase in the number of entries into the open arms (ENTRIES) in relation to males with the same treatment. This result suggests that there is a dimorphic response in coping with physical or emotional stressful situations and that amitriptyline acts in a differential way, being more effective in females.