Local and downstream effects of excitotoxic lesions in the rat medial prefrontal cortex on in vivo 1H-MRS signals

Joshua L. Roffman, Barbara K. Lipska, Alessandro Bertolino, Peter Van Gelderen, Alan W. Olson, Zin Z. Khaing, Daniel R. Weinberger

Research output: Contribution to journalArticle

Abstract

The rat medial prefrontal cortex (mPFC) regulates subcortical dopamine transmission via projections to the striatum and ventral tegmental area. We used in vivo proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to determine whether excitotoxic lesions of the mPFC result in alterations of N-acetylaspartate (NAA), a marker of neuronal integrity, both locally and downstream in the striatum. Lesioned rats exhibited persistent reductions of NAA and other metabolites within the prefrontal cortex; selective reductions of NAA were seen in the striatum, but not in the parietal cortex. Consistent with earlier reports, lesioned rats exhibited a transient enhancement in amphetamine-induced hyperlocomotion. Prefrontal NAA losses correlated with lesion extent. In the striatum, while there was no change in tissue volume, expression of striatal glutamic acid decarboxylase-67 mRNA was significantly reduced. In vivo NAA levels thus appear sensitive to both local and downstream alterations in neuronal integrity, and may signal meaningful effects at cellular and behavioral levels. Copyright (C) 2000 American College of Neuropsychopharmacology.

Original languageEnglish
Pages (from-to)430-439
Number of pages10
JournalNeuropsychopharmacology
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2000

Keywords

  • Glutamic acid decarboxylase-67
  • Ibotenic acid
  • Locomotor activity
  • N-acetylaspartate
  • Prefrontal cortex
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Roffman, J. L., Lipska, B. K., Bertolino, A., Van Gelderen, P., Olson, A. W., Khaing, Z. Z., & Weinberger, D. R. (2000). Local and downstream effects of excitotoxic lesions in the rat medial prefrontal cortex on in vivo 1H-MRS signals. Neuropsychopharmacology, 22(4), 430-439. https://doi.org/10.1016/S0893-133X(99)00143-8