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Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

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 imm...

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Autores principales: Larsson, Markus K, Schwieler, Lilly, Goiny, Michel, Erhardt, Sophie, Engberg, Göran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578548/
https://www.ncbi.nlm.nih.gov/pubmed/26448689
http://dx.doi.org/10.4137/IJTR.S25915
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author Larsson, Markus K
Schwieler, Lilly
Goiny, Michel
Erhardt, Sophie
Engberg, Göran
author_facet Larsson, Markus K
Schwieler, Lilly
Goiny, Michel
Erhardt, Sophie
Engberg, Göran
author_sort Larsson, Markus K
collection PubMed
description 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.
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spelling pubmed-45785482015-10-07 Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid Larsson, Markus K Schwieler, Lilly Goiny, Michel Erhardt, Sophie Engberg, Göran Int J Tryptophan Res Original Research 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. Libertas Academica 2015-09-20 /pmc/articles/PMC4578548/ /pubmed/26448689 http://dx.doi.org/10.4137/IJTR.S25915 Text en © 2016 the author(s), publisher and licensee Libertas Academica Ltd. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.
spellingShingle Original Research
Larsson, Markus K
Schwieler, Lilly
Goiny, Michel
Erhardt, Sophie
Engberg, Göran
Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title_full Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title_fullStr Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title_full_unstemmed Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title_short Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid
title_sort chronic antipsychotic treatment in the rat – effects on brain interleukin-8 and kynurenic acid
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578548/
https://www.ncbi.nlm.nih.gov/pubmed/26448689
http://dx.doi.org/10.4137/IJTR.S25915
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