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Journal of Psychopharmacology
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0269881107081521v1
22/5/536    most recent
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Article

Differential expression of IEG mRNA in rat brain following acute treatment with clozapine or haloperidol: a semi-quantitative RT-PCR study

Melanie J Robbins1*, Hannah M Critchlow1, Andrew Lloyd2, Jackie Cilia1, James Clarke1, Brian Bond2, Declan Jones1, and Peter R Maycox1

1 Department of Biology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, UK.
2 Statistical Sciences Europe, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, UK.

* To whom correspondence should be addressed.


   Abstract

Anti-psychotic drugs have been shown to modulate immediate early gene (IEG) expression in rat brain regions that are associated with schizophrenia, which may be directly linked to their immediate therapeutic benefit. In this study, we analysed the expression profile of a series of IEGs (c-fos, c-jun, fra-1, Krox-20, Krox-24, arc, sgk-1, BDNF and NARP) in six rat brain regions (prefrontal cortex, hippocampus, striatum, nucleus accumbens, thalamus and cerebellum). Rats (n _ 5) were administered either clozapine (20mg/kg i.p.), haloperidol (1mg/kg i.p.) or the appropriate vehicle with pre-treatment times of 1, 6 and 24 h. IEG expression was analysed in these regions by Taqman RT-PCR. The spatial and temporal profile of IEG induction following anti-psychotic drug treatment correlates with regions associated with the efficacy and side effect profile of each drug. In particular, sgk-1 expression levels after anti-psychotic drug treatment may have predictive value when investigating the profile of a novel anti-psychotic drug.

Key Words: anti-psychotic, immediate early genes, schizophrenia, RT-PCR, clozapine, haloperidol

First published on January 21, 2008, doi:10.1177/0269881107081521

Journal of Psychopharmacology 2008;22:536.

A more recent version of this article appeared on July 1, 2008


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