Long-Term Sertraline Intake Reverses the Behavioral Changes Induced by Prenatal Stress in Rats in a Sex-Dependent Way

Abstract

Early life stress is a major factor underlying the vulnerability to respond to stressful events later in life. The present study attempted to evaluate the role of prenatal stress affecting the development of stress-related disorders and their reversion by postnatal exposure to Sertraline (SERT), a front-line medication for medication for posttraumatic stress disorder (PTSD) in humans. To achieve this, adult male and female prenatally stressed (PS) or unstressed (Controls) offspring rats, following oral chronic treatment with SERT (5 mg/kg/day; from 1 month to 4 months old), or not, were studied prior to and after a traumatic event. First, anxiety-like behavior during the prepulse inhibition (PPI) test, a modulation of the startle reflex, was examined in all animals. Subsequently, the animals were subjected to a session of mild inescapable footshocks (IS; 0.35 mA, 5 s) in a shuttle box that was followed by 4 days of situational reminders in the aversive context. Prior to the footshocks no effects of PS or SERT were shown, and no changes in PPI and the habituation to the shuttle box were found. After them, PS led animals to exhibit behavioral alterations. When compared to the Controls, PS animals of both sexes displayed less rearing activity in the aversive environment. PS males responded less to footshock delivery and, in most of the animals, fear extinction was impaired. Moreover, the early postnatal exposure to SERT lessened the behavioral impact of PS in females, while in males it had no effect. Current results extend previous data from our laboratory, showing that PS heightened vulnerability to stress later on, and that SERT acts differently in males and females.

Sex differences in mouse models of fear inhibition: Fear extinction, safety learning, and fear–safety discrimination

“…While footshock pain thresholds are not influenced by sex in C57Bl/6 mice (Podhorna, McCabe, & Brown, ), female rodents, compared to males, are considered more vulnerable to acute stressors (Kokras & Dalla, ). Thus, studies have revealed that the prevalence of jumping is highest among female rodents (Day et al, ; Pereira‐Figueiredo et al, ). In the current study, jumping was exhibited infrequently by males and females across all fear inhibition models tested.…”

Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms

“…Modifications of the PPI are very diverse and may be caused by neurological [ 59 ] or psychiatric diseases characterized by anxiety symptoms [ 60 , 61 ], behavioral states (such as emotional context or a stressor) [ 62 , 63 , 64 ], hormonal levels [ 37 , 65 , 66 ], and even adaptations derived from particularities of some professions, as occurs in the case of athletes [ 67 ]. All reflect various processes of neural plasticity, and it is striking that their sensitivity to sensory events happen a few milliseconds before the startle-eliciting stimulus.…”

Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms

“…Modifications of the PPI are very diverse and may be caused by neurological [48] or psychiatric diseases characterized by anxiety symptoms [49,50], behavioral states (as emotional context or a stressor) [51][52][53], hormonal levels [36,54,55], and even adaptations derived from particularities of some professions, as occurs in the case of athletes [56]. All reflect various processes of neural plasticity, and it is striking that their sensitivity to sensory events happen a few milliseconds before the startle-eliciting stimulus.…”