Differential effects of maternal immune activation and juvenile stress on anxiety-like behaviour and physiology in adult rats: no evidence for the "double-hit hypothesis".

Environmental disruptions can influence neurodevelopment during pre- and postnatal periods. Given such a large time window of opportunity for insult, the "double-hit hypothesis" proposes that exposure to an environmental challenge may impact development such that an individual becomes vulnerable to developing a psychopathology, which then manifests upon exposure to a second challenge later in life. The present study in male rats utilized the framework of the "double-hit hypothesis" to investigate potential compounding effects of maternal immune activation (MIA) during pregnancy and exposure of offspring to stress during juvenility on physiological and behavioural indications of anxiety in adulthood. We used an established rat model of MIA via maternal treatment with polyinosinic:polycytidylic acid (poly I:C) on gestation day 15 in combination with a model of juvenile stress (applied ages 27-29 d) in offspring to explore potential interacting/additive effects. First, we confirmed our employment of the MIA model by replicating previous findings that prenatal treatment with poly I:C caused deficits in sensorimotor gating in adult offspring, as measured by prepulse inhibition. Juvenile stress, on the other hand, had no effect on prepulse inhibition. In terms of anxiety-related behaviour and physiology, we found that prenatal poly I:C alone or in combination with juvenile stress had no effects on body weight, adrenal weight, and plasma concentration of corticosterone and cytokines in adult rats. MIA and juvenile stress increased anxiety-related behaviour on the elevated plus maze, but did so independently of each other. In all, our findings do not support an interaction between MIA and juvenile stress in terms of producing marked changes related to anxiety-like behaviour in adulthood.

Yee N ，Ribic A ，de Roo CC ，Fuchs E ... -  《-》

Immune activation during mid-gestation disrupts sensorimotor gating in rat offspring.

Wolff AR ，Bilkey DK 《BEHAVIOURAL BRAIN RESEARCH》

Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses: implications for the double-hit hypothesis.

Walker AK ，Nakamura T ，Byrne RJ ，Naicker S ，Tynan RJ ，Hunter M ，Hodgson DM ... -  《-》

Prenatal dexamethasone exposure, postnatal development, and adulthood prepulse inhibition and latent inhibition in Wistar rats.

Hauser J ，Feldon J ，Pryce CR 《BEHAVIOURAL BRAIN RESEARCH》

Effects of gestational stress: 1. Evaluation of maternal and juvenile offspring behavior.

Baker S ，Chebli M ，Rees S ，Lemarec N ，Godbout R ，Bielajew C ... -  《BRAIN RESEARCH》