Markus K Larsson, Lilly Schwieler, Michel Goiny, Sophie Erhardt, Göran Engberg
{"title":"Chronic Antipsychotic Treatment in the Rat - Effects on Brain Interleukin-8 and Kynurenic Acid.","authors":"Markus K Larsson, Lilly Schwieler, Michel Goiny, Sophie Erhardt, Göran Engberg","doi":"10.4137/IJTR.S25915","DOIUrl":null,"url":null,"abstract":"<p><p>Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline (n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"8 ","pages":"49-52"},"PeriodicalIF":2.7000,"publicationDate":"2015-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S25915","citationCount":"15","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Tryptophan Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4137/IJTR.S25915","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2015/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 15
Abstract
Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline (n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.
精神分裂症与脑免疫系统的激活有关，这反映在脑尿酸(KYNA)和促炎细胞因子水平的增加上。虽然抗精神病药物已经用于治疗该疾病数十年，但这些药物对大脑免疫信号的潜在影响尚不完全清楚。本研究的目的是探讨抗精神病药物慢性治疗对脑细胞因子和KYNA水平的影响。大鼠每天腹腔注射氟哌啶醇(1.5 mg/kg, n = 6)、奥氮平(2 mg/kg, n = 6)、氯氮平(20 mg/kg, n = 6)或生理盐水(n = 6)，连续30天。与对照组相比，氯氮平治疗的大鼠脑脊液(CSF)白细胞介素-8水平明显降低，氟哌啶醇或奥氮平治疗的大鼠则没有。在任何一组中，全脑的KYNA水平都没有改变。我们的数据表明氯氮平优越的治疗效果可能是其目前显示的免疫抑制作用的结果。此外，我们的数据不支持精神分裂症患者脑KYNA升高是抗精神病药物治疗的结果的可能性。
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
