Sex Differences in the Effects of Sertraline and Stressors in Rats Previously Exposed to Restraint Stress

Abstract

The serotonergic system in the brain plays a major role in mood and anxiety regulation when exposed to stress. The aim of the present study was to evaluate the effects of Sertraline administration in coping with stress using the behavioural paradigms of the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in both sexes. Wistar rats were divided into two groups: intact animals and exposed to restraint stress (RS) 3 times per day during 7 days, which were then subdivided into three other groups: injected with Sertraline (5 mg/kg/day) or the drug vehicle saline for 8 consecutive days, and non-injected. ASR and PPI values were analyzed along 4 sessions to determine behavioral changes. Upon it, we also determine the effects of acute immobilization stress analyzing physiological stress indicators in blood. Our data show sex differences in response to stress paradigms. RS affected more intensely males than females, disturbing the males’ growth and the long-term startle habituation that were not affected in females. PPI increased in the vehicle-injected animals when compared to baseline in both sexes, and Sertraline reversed more efficiently it in females. Moreover, despite both sexes exposed to stressful paradigms exhibited a significant increase in serum glutamic-oxaloacetic transaminase and lactate dehydrogenase enzymes when compared with intact controls, as well as leucopenia, some differences according to sex were found in the haemostatic response to stress. Notably, the repeated injections procedure disturbed the early response to stress, which Sertraline only attenuated in both sexes. Our data suggest that 8-day Sertraline administration is effective in reversing stress-induced changes in some physiological parameters, but insufficient to return immunological values to normality.