Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia

Daniel J. Lodge, Anthony A. Grace

Research output: Contribution to journalArticlepeer-review

281 Scopus citations

Abstract

Evidence supports a dysregulation of subcortical dopamine (DA) system function as acommonetiology of psychosis; however, the factors responsible for this aberrant DA system responsivity have not been delineated. Here, we demonstrate in an animal model of schizophrenia that a pathologically enhanced drive from the ventral hippocampus (vHipp) can result in aberrant dopamine neuron signaling. Adult rats in which development was disrupted by prenatal methylazoxymethanol acetate(MAM)administration display a significantly greater number of spontaneously firing ventral tegmental DA neurons. This appears to be a consequence of excessive hippocampal activity because, in MAM-treated rats, vHipp inactivation completely reversed the elevated DA neuron population activity and also normalized the augmented amphetamine-induced locomotor behavior. These data provide a direct link between hippocampal dysfunction and the hyper-responsivity of the DA system that is believed to underlie the augmented response to amphetamine in animal models and psychosis in schizophrenia patients.

Original languageEnglish (US)
Pages (from-to)11424-11430
Number of pages7
JournalJournal of Neuroscience
Volume27
Issue number42
DOIs
StatePublished - Oct 17 2007

Keywords

  • Animal model
  • Dopamine
  • Hippocampus
  • MAM
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

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