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.

Keywords: behavior; habituation; open field; restrain stress; serotonin; startle.

Figure 1

Effects of prenatal stress and SERT treatment (5 mg/kg/day) on body weight gain (g) over time in females (A) and males (B) (n = 9–11 animals per group and sex). a, p < 0.05 indicates a main effect of prenatal stress; b, p < 0.05, indicates a main effect of SERT in Control-SERT vs. Control (Means ± standard error).

Figure 2

ASR amplitude (in arbitrary units) at P30 and P90 performed in the animals of both sexes subjected or not to prenatal stress (PS and CONTROL), vs. subjected or not to prenatal stress and treated with SERT (Control-SERT and PS-SERT) (5 mg/kg/day). Mean values ± standard error (at P30, n = 18–20 animals per group and sex; at P90, n = 9–11 per group and sex). ¥, p < 0.05 indicates a main effect of sex in all experimental groups.

Figure 3

Effects of prenatal stress and SERT treatment (5 mg/kg/day) on habituation (percentage) in females (A) and males (B) at P90. a, p < 0.05, indicates a main effect of prenatal stress; ¥, p < 0.05, indicates a main effect of sex. Means ± standard error.

Figure 4

Startle latency (stimuli 115 dB) at P30 and P90 in females (A) and males (B). a, p < 0.05 indicates a main effect of prenatal stress in females; ¥, p < 0.05, indicates a main effect of sex in all groups except of PS animals (Fischer LSD test). Mean values ± standard error.

Figure 5

Effects of prenatal stress and SERT treatment on the horizontal activity in the OF test (n = 8–9 per group and sex). Means ± standard error for outer crossing activity (panels A and B) and inner crossing activity (panels C and D) observed, during 3 min sessions on 3 consecutive days. No differences as effect of prenatal stress or SERT-treatment were found in outer crossing activity, F_3,69 = 2.47; or inner crossing activity, F_3,69 = 0.25. ¥, p < 0.05 indicates a main effect of sex on PS animals. *p < 0.05 and ** p < 0.01, indicates a significant increase on both the number of outer and inner crosses in Control females.

Figure 6

Effects of prenatal stress and SERT treatment on the vertical activity in the OF test. Number of rearings observed during 3 min sessions on 3 consecutive days (Panels A and B). Mean values ± standard error. No differences as effect of prenatal stress or SERT-treatment were found, F_3,69 = 0.58, p > 0.05. ¥, p < 0.05 indicates a main effect of sex on PS animals. * p < 0.05, indicates a significant decrease from day 1 to day 2 of test, on the number of rearings in PS-SERT females.

Figure 7

Ratio between inner exploratory activity and outer exploratory activity (IA/OA) on the 1st day of the OF test. a, p < 0.05 indicates a main effect of prenatal stress in males; ¥, p < 0.05 indicates a main effect of sex.