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.
Highlights
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 previously disturbed (PS) females
The serotoninergic system is highly complex, as evidenced by the great diversity of subtypes of receptors on which this neurotransmitter acts and the variety of functions regulated by each receptor subtype (O’Leary et al, 2013). 5-HT presynaptic receptors are located in the dorsal raphe nuclei (DRN) and postsynaptic 5-HT receptors (5-HTR) are largely present in the limbic system (Newport et al, 2001; Hensler, 2003; Leventopoulos et al, 2009)
The main findings of the present study highlight the importance of the exposure during development to environmental challenges affecting the serotonergic system, these effects persisting into adulthood
Summary
Even though there are many children and adolescents with psychiatric disorders (Emslie and Mayes, 2001), decisions regarding the use of antidepressants in young people (such as the SSRIs) are still largely based on data from adults (Manfridi et al, 1992; de Jong et al, 2006). Efficacy measurements in humans recommend SSRIs as the initial medication of choice for young individuals in depression and for improving obsessive-compulsive disorder (OCD; Doogan and Caillard, 1988; Alderman et al, 1998; Emslie and Mayes, 2001; Moreno et al, 2006). SERT seems to be well tolerated in both children and adolescents, with adverse effects similar to those previously reported by adult patients (Alderman et al, 1998; Cook et al, 2001; Skaer et al, 2009). Disturbing serotoninergic homeostasis during its development may result in a changed framework of brain connections and permanent alterations may be induced in adult behavior (Morley-Fletcher et al, 2003; Whitaker-Azmitia, 2005; Ansorge et al, 2008)
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