An augmented dopamine system function is present prior to puberty in the methylazoxymethanol acetate rodent model of schizophrenia

Li Chen, Stephanie M. Perez, Daniel J. Lodge

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Schizophrenia is a disease typically associated with an adolescent onset. Although there have been a considerable number of imaging studies investigating the transition to psychosis in prodromal patients, there are relatively few preclinical studies examining potential mechanisms that may contribute to adolescent onset. We have previously demonstrated, in the methylazoxymethanol acetate (MAM) rodent model of schizophrenia, that an enhanced activity within the ventral hippocampus may underlie the dopamine system hyperfunction, suggested to contribute to positive symptoms in patients. Here we demonstrate that the aberrant regulation of dopamine system function, in MAM-treated rats, is present prior to puberty. Furthermore, we now report that while the afferent regulation of ventral tegmental area dopamine neurons (from the hippocampus and pedunculopontine tegmental area) appears intact in preadolescent rats, the behavioral response to alterations in dopamine system function appears to be attenuated in preadolescent rats. Thus, we posit that the pathological alterations underlying psychosis may be present prior to symptom onset and that the "normal" development of the postsynaptic side of the dopamine system may underlie the transition to psychosis.

Original languageEnglish (US)
Pages (from-to)907-917
Number of pages11
JournalDevelopmental Neurobiology
Volume74
Issue number9
DOIs
StatePublished - Sep 2014

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Keywords

  • Hippocampus
  • MAM rat
  • Parvalbumin
  • Preadolescent
  • Schizophrenia

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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