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


OBJECTIVE
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.
Department of Psychology, Tel Aviv University, 69978, Tel Aviv, Israel.
Lee
L
Zuckerman
Ina
I
Weiner
D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological; D004622:Embryo, Mammalian / Q000276:immunology*; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D007266:Inhibition, Psychological; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013194:Staining and Labeling
D011070:Poly I-C