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

Neurotoxicol Teratol. Jan-Feb 2015;47:54-65. doi: 10.1016/j.ntt.2014.10.007. Epub 2014 Nov 8.

Abstract

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.

Keywords: (+)-Amphetamine-induced locomotor activity; MK-801-induced locomotor activity; Morris water maze; Polyinosinic–polycytidylic acid; Prenatal immune activation; Rat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Adaptation, Ocular / drug effects
  • Age Factors
  • Amphetamine / pharmacology*
  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Conditioning, Psychological / drug effects
  • Dizocilpine Maleate / pharmacology*
  • Exploratory Behavior / drug effects
  • Fear / drug effects
  • Female
  • Interferon Inducers / toxicity*
  • Litter Size / drug effects
  • Male
  • Maze Learning / drug effects
  • Neuroprotective Agents / pharmacology
  • Poly I-C / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / immunology
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Prepulse Inhibition / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sex Ratio
  • Spatial Learning / drug effects*

Substances

  • Interferon Inducers
  • Neuroprotective Agents
  • Dizocilpine Maleate
  • Amphetamine
  • Poly I-C