The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

Abstract

Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.

Sex-Dependent Effects of Prenatal Stress on Learned Helplessness and Anxiety-Related Behaviours in Wistar Rats

“…However, we found no differences in the locomotor activity as effect of SERT administration. This supports previous results [13] [51] [54] in which fluoxetine or SERT reduced the stressinduced immobility, without influencing other activities.…”

“…Only offspring from litters containing 9 -12 pups were used in the present experiments. Offspring were weaned at 21 days of age and were separated into group cages housing four animals of the same sex and treatment as previously described [13]. No differences in litter sizes, in the male-to-female ratio of the offspring or inpre-weaning-mortality were found.…”

“…Based on previous reports [13], we decided to administer SERT orally (Besitran © Pfizer S. A. Madrid, Spain) at a dose of 5.0 mg/kg/day. Liquid consumption was controlled by using calibrated bottles, and was monitored every two days, and the dose of the drug was adjusted on the basis of the liquid consumed.…”

Prenatal stress and early‐life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring

“…In addition, exposure to both prenatal SSRIs and maternal depression can increase internalizing behaviors (depression, anxiety, and withdrawal) in 3 and 4 year olds (Oberlander et al, ). Preclinical studies have also demonstrated that developmental SSRI exposure can have long term effect on affective‐like behaviors in offspring with a well‐documented increase in both anxiety‐ and depression‐related behaviors, particularly in adult male offspring, after prenatal or early postnatal treatment with SSRIs (Ansorge, Zhou, Lira, Hen, & Gingrich, ; Karpova, Lindholm, Pruunsild, Timmusk, & Castren, ; Lisboa, Oliveira, Costa, Venancio, & Moreira, ; Noorlander et al, ; Olivier et al, ; Popa, Lena, Alexandre, & Adrien, ; Smit‐Rigter et al, ), however, this is not always the case and often minimal long‐term effects of perinatal SSRI exposure has been reported (Nagano, Liu, Inagaki, Kawada, & Suzuki, ; Pereira‐Figueiredo, Sancho, Carro, Castellano, & Lopez, ). It should be noted that the majority of these studies did not investigate the effect of perinatal SSRI exposure using a model of maternal depression.…”

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

“…Based on previous reports (Pereira-Figueiredo et al, 2014, 2015), SERT was given orally (Besitran© Pfizer S.A. Madrid, Spain) at a dose of 5.0 mg/kg/day. Using calibrated bottles, which were monitored every 2 days, liquid consumption was controlled, and the dose of the drug was adjusted on the basis of the liquid consumed and mean body weight.…”