Department of Biology, Faculty of Science, Erciyes University, Kayseri, Turkey.
Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Fundam Clin Pharmacol. 2024 Dec;38(6):1069-1079. doi: 10.1111/fcp.13028. Epub 2024 Jul 4.
Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic-polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring.
The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C-induced schizophrenia-like model in rats.
For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL-6 levels after 2 h. At postnatal days 83-86, behavioral tests were performed.
Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open-field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69-83) caused significant improvements in these deficits.
Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.
多项研究明确证实，孕妇在妊娠期间接触各种感染与精神分裂症风险增加有关。在临床前研究中，给怀孕的啮齿动物施用聚肌胞苷酸（Poly I:C）可引发母体免疫激活，导致后代大脑功能受损。
本研究旨在探讨文拉法辛（一种多模式选择性 5-羟色胺再摄取抑制剂（SSRI））在聚肌胞苷酸诱导的精神分裂症样大鼠模型的病理生理学中的作用。
为此，在交配后第 14 天，将聚肌胞苷酸（8mg/kg，ip）注入怀孕动物体内，并在 2 小时后取尾血以测定白细胞介素 6 （IL-6）水平。在产后第 83-86 天，进行行为测试。
我们的结果表明，聚肌胞苷酸导致预脉冲抑制、新物体识别、社会互动和旷场试验受损。文拉法辛（2.5、5 和 10mg/kg，ip，产后第 69-83 天）的慢性给药导致这些缺陷显著改善。
总体而言，我们的发现表明文拉法辛可能为精神分裂症的治疗提供新的治疗方法。我们认为额叶脑区 5-羟色胺能活性的增加可能提供文拉法辛的改善作用，特别是对阴性和认知症状。因此，通过进一步的研究，确定文拉法辛与联合药物的疗效将是有用的。
