TY - JOUR
T1 - Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring
AU - Zuckerman, Lee
AU - Weiner, Ina
N1 - Funding Information:
We thank Novartis Switzerland for their gift of clozapine. This research was partly supported by the Adams Super-Center for Brain Studies, Tel-Aviv University, and the Israel Foundations Trustees award to L. Zuckerman.
PY - 2005/5
Y1 - 2005/5
N2 - Maternal exposure to viral infection has been associated with an increased risk of schizophrenia in the offspring, and it has been suggested that the maternal immune response may interfere with normal fetal brain development. Although studies in rodents have shown that perinatal viral infections can lead to neuropathological and behavioral abnormalities considered relevant to schizophrenia, it is not clear whether these consequences are due to the infection itself or to the maternal immune response to infection. We show that an induction of maternal immune stimulation without exposure to a virus by injecting pregnant dams with the synthetic cytokine releaser polyriboinosinic-polyribocytidilic acid (poly I:C) leads to abnormal behavioral and pharmacological responses in the adult offspring. As in schizophrenia, these offspring displayed excessive behavioral switching, manifested in the loss of latent inhibition and in rapid reversal learning. Consistent with the clinical pharmacology of schizophrenia, both deficits were alleviated by antipsychotic treatment. In addition, these offspring displayed increased sensitivity to the locomotor-stimulating effects of MK-801, pointing to developmental alterations of the dopaminergic and/or glutamatergic systems. Prenatal poly I:C administration did not produce learning deficits in classical fear conditioning, active avoidance, discrimination learning and water maze. These results show that the maternal immune response is sufficient to cause behavioral and pharmacological alterations relevant to schizophrenia in the adult offspring.
AB - Maternal exposure to viral infection has been associated with an increased risk of schizophrenia in the offspring, and it has been suggested that the maternal immune response may interfere with normal fetal brain development. Although studies in rodents have shown that perinatal viral infections can lead to neuropathological and behavioral abnormalities considered relevant to schizophrenia, it is not clear whether these consequences are due to the infection itself or to the maternal immune response to infection. We show that an induction of maternal immune stimulation without exposure to a virus by injecting pregnant dams with the synthetic cytokine releaser polyriboinosinic-polyribocytidilic acid (poly I:C) leads to abnormal behavioral and pharmacological responses in the adult offspring. As in schizophrenia, these offspring displayed excessive behavioral switching, manifested in the loss of latent inhibition and in rapid reversal learning. Consistent with the clinical pharmacology of schizophrenia, both deficits were alleviated by antipsychotic treatment. In addition, these offspring displayed increased sensitivity to the locomotor-stimulating effects of MK-801, pointing to developmental alterations of the dopaminergic and/or glutamatergic systems. Prenatal poly I:C administration did not produce learning deficits in classical fear conditioning, active avoidance, discrimination learning and water maze. These results show that the maternal immune response is sufficient to cause behavioral and pharmacological alterations relevant to schizophrenia in the adult offspring.
KW - Cytokines
KW - Latent inhibition
KW - Maternal immune activation
KW - Neurodevelopment
KW - Poly I:C
KW - Reversal learning
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=13844276635&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2004.08.008
DO - 10.1016/j.jpsychires.2004.08.008
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:13844276635
SN - 0022-3956
VL - 39
SP - 311
EP - 323
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
IS - 3
ER -