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0269881106062025v1
20/5/636    most recent
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This version was published on September 1, 2006
Journal of Psychopharmacology, Vol. 20, No. 5, 636-642 (2006)
DOI: 10.1177/0269881106062025

Selective increases in the cytokine, TNF{alpha}, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs

G. J. Paterson

Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK

Y. Ohashi

Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK.; Mitsubishi Pharma Corp., 1000, Kamoshida-cho, Yokohama, Japan gary.patterson{at}invitrogen.com

G. P. Reynolds

Department of Biomedical Science, University of Sheffield, Sheffield, UK.; Dept. of Mental Health, Queen's University, Whitla Medical Building, 97 Lisburn Rd, Belfast, BT9 7BL

J. A. Pratt

Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK. Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK

B. J. Morris

Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK

The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF 1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.

Key Words: TNF{alpha} • psychosis • prefrontal cortex • cytokines • schizophrenia


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