The neonatal ventral hippocampal lesion model of schizophrenia: Effects on dopamine and GABA mRNA markers in the rat midbrain

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

Research output: Contribution to journalArticle

Abstract

The neonatal ventral hippocampal lesion in the rat has been used as a model of schizophrenia, a human disorder associated with changes in markers of dopamine and γ-aminobutyric acid (GABA) circuits in various regions of the brain. We investigated whether alterations in mRNA markers related to the activity of midbrain dopaminergic and GABAergic neurons are associated with this model. We used in situ hybridization histochemistry to assess expression of mRNAs for dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase-67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood significantly reduced expression of DAT mRNA in the substantia nigra and the ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in these midbrain regions. Adult lesioned rats showed no changes in the expression of any of these genes. As the neonatal ventral hippocampal lesion reproduces many aspects of schizophrenia and is used as an animal model of this disorder, these results suggest that the reduction in DAT mRNA could result from developmental neuropathology in the ventral hippocampus and may thus represent a molecular substrate of the disease process.

Original languageEnglish (US)
Pages (from-to)3097-3104
Number of pages8
JournalEuropean Journal of Neuroscience
Volume18
Issue number11
DOIs
StatePublished - 2003
Externally publishedYes

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Mesencephalon
gamma-Aminobutyric Acid
Dopamine
Schizophrenia
Dopamine Plasma Membrane Transport Proteins
Tyrosine Decarboxylase
Messenger RNA
Glutamate Decarboxylase
Tyrosine 3-Monooxygenase
Hippocampus
Ibotenic Acid
Aminobutyrates
GABAergic Neurons
Ventral Tegmental Area
Dopaminergic Neurons
Substantia Nigra
In Situ Hybridization
Animal Models
Gene Expression
Brain

Keywords

  • Animal model
  • Dopamine
  • Dopamine transporter
  • GAD-67
  • Schizophrenia
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The neonatal ventral hippocampal lesion model of schizophrenia : Effects on dopamine and GABA mRNA markers in the rat midbrain. / Lipska, Barbara K.; Lerman, Daniel N.; Khaing, Zin Z.; Weinberger, Daniel.

In: European Journal of Neuroscience, Vol. 18, No. 11, 2003, p. 3097-3104.

Research output: Contribution to journalArticle

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