Department of Neurobiology, GELIFES, University of Groningen, Nijenborgh 7, 9747, AG, Groningen, the Netherlands.
Psychopharmacology (Berl). 2020 Sep;237(9):2589-2600. doi: 10.1007/s00213-020-05535-7. Epub 2020 Jul 17.
Many depressed women continue antidepressant treatment during pregnancy. Selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy increases the risk for abnormal social development of the child, including increased aggressive or defiant behavior, with unknown effects on sexual behavior.
Our aim was to investigate the effects of perinatal SSRI treatment and maternal depression, both separately and combined, on aggressive and sexual behavior in male rat offspring.
Heterozygous serotonin transporter (SERT ) knockout dams exposed to early life stress (ELSD) were used as an animal model of maternal depression. Early life stress consisted of separating litters from their mother for 6 h a day on postnatal day (PND)2-15, resulting in a depressive-like phenotype in adulthood. Depressive-like dams were treated with fluoxetine (FLX, 10 mg/kg) or vehicle throughout pregnancy and lactation (gestational day 1 until PND 21). Male offspring were tested for aggressive and sexual behavior in adulthood. As lifelong reductions in SERT expression are known to alter behavioral outcome, offspring with normal (SERT) and reduced (SERT ) SERT expression were assessed.
Perinatal FLX treatment reduced offensive behavior and the number of animals attacking and increased the latency to attack, especially in SERT offspring. Perinatal FLX treatment reduced the mounting frequency in SERT offspring. ELSD increased offensive behavior, without affecting sexual behavior in SERT offspring.
Overall, our research demonstrates that perinatal FLX treatment and ELSD have opposite effects on aggressive behavior, with little impact on sexual behavior of male offspring.
许多抑郁的女性在怀孕期间继续接受抗抑郁药物治疗。选择性 5-羟色胺再摄取抑制剂(SSRIs)在怀孕期间的治疗会增加儿童异常社会发展的风险,包括增加攻击性或挑衅行为,但其对性行为的影响尚不清楚。
我们旨在研究围产期 SSRI 治疗和母体抑郁,单独及联合治疗,对雄性大鼠后代的攻击和性行为的影响。
杂合性 5-羟色胺转运体(SERT)敲除的孕鼠暴露于早期生活应激(ELSD),作为母体抑郁的动物模型。早期生活应激包括在产后第 2-15 天每天将幼崽与母亲分开 6 小时,导致成年后出现抑郁样表型。有抑郁样表现的孕鼠在整个孕期和哺乳期(妊娠第 1 天至 PND21)接受氟西汀(FLX,10mg/kg)或载体处理。雄性后代在成年期进行攻击和性行为测试。由于 SERT 表达的终生减少已知会改变行为结果,因此评估了具有正常(SERT)和减少(SERT)SERT 表达的后代。
围产期 FLX 治疗可减少攻击性行为和攻击动物的数量,并增加攻击潜伏期,尤其是在 SERT 后代中。围产期 FLX 治疗降低了 SERT 后代的交配频率。ELSD 增加了攻击性行为,但对 SERT 后代的性行为没有影响。
总的来说,我们的研究表明,围产期 FLX 治疗和 ELSD 对攻击性行为有相反的影响,对雄性后代的性行为影响很小。