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

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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 schizophrenia.

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Acknowledgements

We gratefully acknowledge the help of Drs. Raya Eilam and Tamar Kadar in the histological assessment. This research was partly supported by Adams Super-Center for Brain Studies, Tel-Aviv University, and the Israel Foundation Trustees award to L.Z.

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  1. Department of Psychology, Tel Aviv University, 69978, Tel Aviv, Israel

    Lee Zuckerman & Ina Weiner

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  1. Lee Zuckerman
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  2. Ina Weiner
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Correspondence to Ina Weiner.

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Zuckerman, L., Weiner, I. Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation. Psychopharmacology 169, 308–313 (2003). https://doi.org/10.1007/s00213-003-1461-7

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  • DOI: https://doi.org/10.1007/s00213-003-1461-7

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