Effects of early vs. late maternal immune activation on schizophrenia-like behaviour in adult rat offspring

Abstract

Exposure to prenatal infection is associated with increased risk for schizophrenia in offspring, an effect that is believed to be primarily mediated by the maternal immune response. Many previous studies have established that maternal immune activation (MIA) via the viral mimic Poly(I:C) in pregnant rodents leads to a variety of schizophrenia-related behavioural consequences in rat or mouse offspring. In the current study, we aimed to establish a similar model in our laboratory, by exposing rats to Poly(I:C) at either early or late gestation and investigating schizophrenia-related behaviours in the adult offspring. Pregnant Wistar rats were exposed to 4 mg/kg Poly(I:C) (MIA) or saline (Control) at gestational day 10 (GD10) or GD19. As adults, males, but not females, exposed to MIA (regardless of GD) exhibited reductions in sensorimotor gating. In addition, transient working memory impairments were observed in GD19, but not GD10 rats exposed to MIA (regardless of sex). MIA did not affect the sensitivity of rats to the locomotor-enhancing effects of MK-801 or amphetamine. This study demonstrates that MIA at early and late gestation in Wistar rats produces behavioural alterations that are subtle, compared to previous reports using other species, or GDs of MIA.