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

J Psychopharmacol. 2008 Jul;22(5):536-42. doi: 10.1177/0269881107081521. Epub 2008 Jan 21.

Abstract

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.

MeSH terms

  • Animals
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Clozapine / adverse effects
  • Clozapine / pharmacology*
  • Gene Expression Regulation / drug effects
  • Genes, Immediate-Early / drug effects*
  • Haloperidol / adverse effects
  • Haloperidol / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Time Factors

Substances

  • Antipsychotic Agents
  • RNA, Messenger
  • Clozapine
  • Haloperidol