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The Journal of Neuroscience, January 1, 2003, 23(1):297-302
Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring
Limin Shi1, S. Hossein Fatemi2, Robert W. Sidwell3, and Paul H. Patterson1 1 Biology Division, California Institute of Technology, Pasadena, California 91125, 2 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota 55455, and 3 Institute for Antiviral Research, Utah State University, Logan, Utah 84322
Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
Key words: schizophrenia; autism; mental retardation; prepulse inhibition; acoustic startle; open field; novel object; clozapine; chlorpromazine; ketamine; poly(I:C)
Copyright © 2003 Society for Neuroscience 0270-6474/03/231297-06$05.00/0
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