Vortioxetine improved schizophrenia-like behavioral deficits in a Poly I:C-induced maternal immune activation model of schizophrenia in rats

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-07-04 DOI:10.1111/fcp.13028
Mehmet Taskiran, Sacide Yildiz Taskiran, Gokhan Unal, Nuh Mehmet Bozkurt, Asuman Golgeli
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Abstract

Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

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伏替西汀可改善 Poly I:C 诱导的母体免疫激活大鼠精神分裂症模型中类似精神分裂症的行为缺陷。
背景:多项研究清楚地表明,孕期受到各种感染与精神分裂症风险的增加有关。在临床前研究中,妊娠啮齿动物服用多聚肌苷酸(Poly I:C)可诱发母体免疫激活,导致后代大脑功能受损:本研究旨在探讨多模式选择性5-羟色胺再摄取抑制剂(SSRI)伏替西汀对Poly I:C诱导的大鼠精神分裂症样模型病理生理学的影响:为此,在交配 14 天后向妊娠动物注射 Poly I:C(8 毫克/千克,ip),2 小时后抽取尾血测定 IL-6 水平,并在出生后第 83-86 天进行行为测试:结果:我们的研究结果表明,Poly I:C会导致动物在前脉冲抑制、新物体识别、社会交往和开阔地测试中出现障碍。长期服用伏替西汀(2.5、5和10毫克/千克,ip,出生后第69-83天)可显著改善这些缺陷:总之,我们的研究结果表明,伏替西汀可能为精神分裂症的治疗提供新的治疗方法。我们认为,额叶脑区血清素能活动的增加可能会使伏替西汀产生改善作用,尤其是对阴性症状和认知症状。因此,进一步的研究将有助于确定伏替西汀与联合药物的疗效。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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