Gene expression in dopamine and GABA systems in an animal model of schizophrenia: Effects of antipsychotic drugs

Barbara K. Lipska, Daniel N. Lerman, Zin Z. Khaing, Cynthia Shannon Weickert, Daniel Weinberger

Research output: Contribution to journalArticle

Abstract

We used in situ hybridization histochemistry to assess expression of dopamine receptors (D1R, D2R and D3R), neurotensin, proenkephalin and glutamate decarboxylase-67 (GAD67) in the prefrontal cortex, striatum, and/or nucleus accumbens in adult rats with neonatal ventral hippocampal (VH) lesions and in control animals after acute and chronic treatment with antipsychotic drugs clozapine and haloperidol. We also acquired these measures in a separate cohort of treatment-naïve sham and neonatally VH-lesioned rats used as an animal model of schizophrenia. Our results indicate that the neonatal VH lesion did not alter expression of D1R, D3R, neurotensin or proenkephalin expression in any brain region examined. However, D2R mRNA expression was down-regulated in the striatum, GAD67 mRNA was down-regulated in the prefrontal cortex and prodynorphin mRNA was up-regulated in the striatum of the VH-lesioned rats as compared with sham controls. Antipsychotic drugs did not alter expression of D1R, D2R or D3R receptor mRNAs but elevated neurotensin and proenkephalin expression in both groups of rats; patterns of changes were dependent on the duration of treatment and brain area examined. GAD67 mRNA was up-regulated by chronic antispychotics in the nucleus accumbens and the striatum and by chronic haloperidol in the prefrontal cortex in both sham and lesioned rats. These results indicate that the developmental VH lesion changed the striatal expression of D2R and prodynorphin and robustly compromised prefrontal GAD67 expression but did not modify drug-induced expression of any genes examined in this study.

Original languageEnglish (US)
Pages (from-to)391-402
Number of pages12
JournalEuropean Journal of Neuroscience
Volume18
Issue number2
DOIs
Publication statusPublished - 2003
Externally publishedYes

    Fingerprint

Keywords

  • Clozapine
  • Dopamine receptors
  • GAD-67
  • Haloperidol
  • Neurotensin
  • Prodynorphin
  • Proenkephalin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this