Prenatal immune challenge in rats: Effects of polyinosinic–polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine

Dec 3, 2014Neurotoxicology and teratology

Prenatal Immune Activation in Rats: Effects of a Viral-Like Trigger on Memory, Sensory Filtering, Fear Learning, and Drug Responses

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Abstract

Offspring from mothers with the highest immune activation may exhibit more severe behavioral effects.

Prenatal exposure to the immune activator Poly IC in rats was linked to varying behavioral outcomes based on maternal weight change.
Males from the high weight gain group (Poly IC (H)) showed decreased response to loud sounds, while females from the low weight gain group (Poly IC (L)) exhibited reduced response and increased prepulse inhibition.
Hyperactivity in offspring was pronounced in response to amphetamine, particularly in the Poly IC (H) group, while a reduced hyperactivity response was noted in the Poly IC (L) group following MK-801 exposure.
Reduced cued conditioned freezing was observed in Poly IC (L) males, and both sexes spent less time in darkness during light-dark tests.
Impaired performance was noted in the Morris water maze for offspring from both Poly IC groups, indicating challenges in learning the location of hidden platforms.

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Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior.

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Prenatal immune challenge in rats: Effects of polyinosinic–polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine

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