Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring.
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.
Zuckerman
Lee
L
Department of Psychology, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel.
Weiner
Ina
I
D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000009:adverse effects; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000009:adverse effects; D007112:Immunity, Maternally-Acquired / Q000187:drug effects*; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D011070:Poly I-C / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D011070:Poly I-C; D004298:Dopamine