Excitotoxic lesions of the rat medial prefrontal cortex: Effects on abnormal behaviors associated with neonatal hippocampal damage

Barbara K. Lipska, Hassen A. Al-Amin, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

Abstract

Neonatal excitotoxic damage of the ventral hippocampus (VH) is a heuristic model of schizophrenia. We investigated whether: (1) neonatal damage of the medial prefrontal cortex (mPFC) has effects similar to the neonatal VH lesion; and (2) intrinsic mPFC neurons contribute to the abnormal behaviors associated with VH lesions. Neonatal rats were lesioned in the mPFC. In adulthood, they showed attenuated locomotion in response to novelty, amphetamine, and MK-801, and enhanced apomorphine-induced stereotypies as compared to controls. Striatal D1 and D2 receptor mRNAs were unaltered. Another group was lesioned in the VH and additionally in the mPFC in adulthood. Destroying mPFC neurons normalized hyperlocomotion to novelty and amphetamine of the neonatally VH lesioned rats. Thus, neonatal damage of the mPFC does not provide a heuristic model of schizophrenia-like phenomena, in contrast to analogous damage of the VH. However, mPFC intrinsic neurons that have developed in the context of abnormal hippocampal connectivity may be responsible for abnormal behaviors in the neonatally VH lesioned rats. Copyright (C) 1998 American College of Neuropsychopharmacology.

Original languageEnglish (US)
Pages (from-to)451-464
Number of pages14
JournalNeuropsychopharmacology
Volume19
Issue number6
DOIs
StatePublished - Dec 1998
Externally publishedYes

Keywords

  • Amphetamine
  • Animal models
  • Apomorphine
  • Ibotenic acid
  • MK-801
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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