Neonatal lesions of the ventral hippocampal formation alter GABA-A receptor subunit mRNA expression in adult rat frontal pole

Colin P. Mitchell, Dennis R. Grayson, Morris B. Goldman

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Gamma-aminobutyric acid (GABA)-ergic function is altered in schizophrenia. Of particular interest is the altered central nervous system expression of GABA-A receptor subunits, as changes in subunit expression account for recognized differences in mammalian brain function making them inviting targets for novel psychotropic agents. Excitotoxic neonatal lesions of the ventral hippocampal formation (NVHL) in rats reproduce numerous aspects of schizophrenia, including decreased mRNA expression of the GABA synthesizing enzyme glutamic acid decarboxylase-67, though their impact on subunit expression is unknown. We utilized quantitative reverse transcription polymerase chain reaction to investigate mRNA expression of the α1, α5, and γ2s GABA-A receptor subunits in the frontal pole of water-deprived adult NVHL and SHAM-lesioned animals. Messenger RNA expression for all three GABA-A subunits (α1-NVHL: 18.5 ± 1.6 pg/μg total pooled RNA, SHAM: 11.3 ±. 4; α5-NVHL: 5.1 ±. 6; SHAM: 3.5 ±. 7; and γ2s-NVHL: 10.8 ± 1.7; SHAM: 7.2 ± 1.5) was higher in NVHL, though only levels of α1 differed significantly after correction for multiple comparisons. Levels of a control mRNA, neuronal specific enolase, were similar in the two groups. These data indicate that NVHL reproduce changes in cortical GABA-A receptor subunit expression seen in schizophrenia, suggesting this animal model may facilitate efforts to clarify the physiologic significance of altered GABA function and to develop novel targets for therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalBiological psychiatry
Volume57
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • GABA
  • Hippocampus
  • benzodiazepine
  • quantitative RT- PCR
  • schizophrenia
  • ventral hippocampus

ASJC Scopus subject areas

  • Biological Psychiatry

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