Differential expression of IEG mRNA in rat brain following acute treatment with clozapine or haloperidol: a semi-quantitative RT-PCR study.
Antipsychotic 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 (20 mg/kg i.p.), haloperidol (1 mg/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 antipsychotic drug treatment correlates with regions associated with the efficacy and side effect profile of each drug. In particular, sgk-1 expression levels after antipsychotic drug treatment may have predictive value when investigating the profile of a novel antipsychotic drug.
Robbins
M J
MJ
Department of Biology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, UK. melanie_j_robbins@gsk.com
Critchlow
H M
HM
Lloyd
A
A
Cilia
J
J
Clarke
J D
JD
Bond
B
B
Jones
D N C
DN
Maycox
P R
PR
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects*; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D003024:Clozapine; D006220:Haloperidol