Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation

Lee Zuckerman, Ina Weiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Rationale: There is evidence pointing to an association between prenatal exposure to infection and increased liability to schizophrenia, and it has been suggested that the maternal immune response, in particular, the release of pro-inflammatory cytokines, may interfere with normal fetal brain development. Impaired capacity to ignore irrelevant stimuli is considered one of the central deficits in schizophrenia, and is manifested, among others, in disrupted latent inhibition (LI). Objectives: To test the effects of prenatal immune activation on LI in juvenile and adult offspring. Methods: Pregnant rats were injected with the synthetic cytokine releaser polyriboinosinic-polyribocytidilic acid (poly I:C, 4 mg/kg) on gestational day 15. LI was assessed in 35-day and 3-month-old offspring using a thirst motivated conditioned emotional response procedure. Results: Consistent with the characteristic maturational delay of schizophrenia, prenatal immune activation did not affect LI in the juvenile offspring but led to a post-pubertal emergence of LI disruption. In addition, pronounced alterations in hippocampal morphology resembling those found in schizophrenia, were evident in the adult offspring. Conclusions: These results support the hypothesis that immune activation during pregnancy may lead to long-term abnormalities mimicking those observed in schizo-phrenia.

Original languageEnglish
Pages (from-to)308-313
Number of pages6
JournalPsychopharmacology
Volume169
Issue number3-4
DOIs
StatePublished - Sep 2003

Funding

FundersFunder number
Adams Super-Center for Brain Studies
Tel-Aviv University
State Trustees Australia Foundation

    Keywords

    • Cytokines schizophrenia
    • Hippocampus
    • Latent inhibition
    • Neurodevelopment
    • Poly I:C

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