Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences Bratislava, Slovakia.
Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences Bratislava, Slovakia; Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
Behav Brain Res. 2021 Feb 1;398:112944. doi: 10.1016/j.bbr.2020.112944. Epub 2020 Oct 3.
Preclinical studies suggest that stress-related disorders even prior gestation can cause long-term changes at the level of neurobehavioral adaptations. Therefore, it is critical to consider undergoing antidepressant therapy which could reverse the negative consequences in the offspring. Venlafaxine is widely used in clinical practice; however insufficient amount of well-controlled studies verified the safety of venlafaxine therapy during gestation and lactation. The aim of this work was to investigate the effects of perinatal venlafaxine therapy on selected neurobehavioral variables in mothers and their female offspring using a model of maternal adversity. Pre-gestational stressed and non-stressed Wistar rat dams were treated with either venlafaxine (10 mg/kg/day) or vehicle during pregnancy and lactation. We have shown that pre-gestational stress decreased the number of pups with a significant reduction in the number of males but not females. Furthermore, we found that offspring of stressed and treated mothers exhibited anxiogenic behavior in juvenile and adolescent age. However, during adulthood pre-gestational stress significantly increased anxiety-like behavior of female, with venlafaxine treatment normalizing the state to control levels. Additionally, we found that even maternal stress prior gestation can have long-term impact on adult number of hippocampal immature neurons of the female offspring. A number of questions related to the best treatment options for maternal depression still remains, however present data may provide greater insight into the possible outcomes associated with perinatal venlafaxine therapy.
临床前研究表明，即使在妊娠前，与压力相关的疾病也会导致神经行为适应层面的长期变化。因此，考虑进行抗抑郁治疗以逆转后代的负面影响至关重要。文拉法辛在临床实践中被广泛应用；然而，只有数量有限的对照良好的研究证实了妊娠和哺乳期使用文拉法辛治疗的安全性。本研究旨在使用母体逆境模型，调查围产期文拉法辛治疗对母体及其雌性后代某些神经行为变量的影响。在妊娠和哺乳期，未受孕应激和未应激的 Wistar 大鼠母体接受文拉法辛（10mg/kg/天）或载体处理。我们发现，受孕前应激降低了幼仔数量，雄性幼仔数量显著减少，但雌性幼仔数量没有减少。此外，我们发现应激和处理后的母亲的后代在青少年时期表现出焦虑样行为。然而，在成年期，受孕前应激显著增加了雌性的焦虑样行为，而文拉法辛治疗使这种状态恢复到对照水平。此外，我们发现即使是受孕前的母体应激也会对雌性后代成年期海马未成熟神经元的数量产生长期影响。与围产期文拉法辛治疗相关的最佳治疗选择仍存在许多问题，但目前的数据可能为可能的结果提供更深入的了解。
