Pereira-Figueiredo Inês, Sancho Consuelo, Carro Juan, Castellano Orlando, López Dolores E
Neuroscience Institute of Castilla y León (INCYL), University of Salamanca Salamanca, Spain.
Neuroscience Institute of Castilla y León (INCYL), University of Salamanca Salamanca, Spain ; Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca Salamanca, Spain ; Department of Physiology and Pharmacology, University of Salamanca Salamanca, Spain.
Front Behav Neurosci. 2014 Aug 6;8:260. doi: 10.3389/fnbeh.2014.00260. eCollection 2014.
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.
舍曲林(SERT)是一种临床有效的选择性5-羟色胺再摄取抑制剂(SSRI),已知可提高并稳定5-羟色胺水平。这种神经递质在啮齿动物和人类的青少年大脑发育中都起着重要作用,其失调与行为和情绪调节方面的缺陷相关。由于产前应激可能扰乱5-羟色胺能稳态,本研究的目的是检查在整个青春期给予SERT对产前应激的Wistar大鼠行为和生理发育参数的长期影响。对一半妊娠母鼠(无论是否通过束缚应激)所产的雌雄后代,从1至3月龄开始给予SERT(5mg/kg/天,口服)。我们的数据显示,长期SERT治疗使雌雄两性的体重增加略有减少,但逆转了在产前应激雌性大鼠中发现的发育受扰的“追赶”生长。产前应激和SERT治疗均未引起行为上的显著改变,且对平均惊跳反射值无影响。然而,发现了产前应激对性别的依赖性影响:在雄性大鼠中,产前应激模式使旷场试验中的焦虑样行为略有增加,而在雌性大鼠中,则损害了惊跳习惯化。在这两种情况下,SERT治疗均逆转了这些现象。此外,产前应激动物的两性白细胞谱均受到干扰,而SERT使其得到逆转。目前的研究结果证明,在啮齿动物中,从青春期到成年期持续给予SERT是安全的,并且可以减轻产前应激对大鼠的影响。