Effects of Cohabitation on Neurodevelopmental Outcomes in Rats Discordant for Neonatal Exposure to Sevoflurane

Having a sibling with autism spectrum disorder (ASD) is risk factor for ASD. We used a rat model in which the general anesthetic sevoflurane (SEVO) induces ASD-like neurodevelopmental abnormalities to test whether they can be transmitted via cohabitation. Male rat pups from several litters were mixed and randomized to three new litter types: SEVO-exposed (SEVO); SEVO-unexposed (Control); and equal numbers of SEVO-exposed and -unexposed (MIXED). After weaning, rats in Experiment 1 were housed with littermates in SEVO, Control, and MIXED (MIXED-exposed and MIXED-unexposed) pairs. In Experiment 2, MIXED-exposed and MIXED-unexposed rats were paired with an unfamiliar naïve cagemate. Corticosterone levels, gene expression, central inflammatory markers (Experiment 1) and behavior and corticosterone levels (Experiment 2) were assessed in adulthood. In Experiment 1, SEVO rats, when compared to Control rats, exhibited abnormalities in hypothalamic-pituitary-adrenal axis, inflammatory markers, oxytocin, arginine-vasopressin, and DNA methylation systems. Almost all these measures in MIXED-exposed and MIXED-unexposed rats were statistically indistinguishable and were similar to those either in SEVO or Control rats, with the majority of measures in MIXED rats being similar to those in SEVO rats. Experiment 2 showed that pairing with unfamiliar, naïve rats after weaning caused MIXED-unexposed and MIXED-exposed rats' behavior to be no different from Control and SEVO rats, respectively; however, MIXED rats also did not differ from each other. These findings suggest that neurodevelopmental abnormalities can be transmitted to otherwise healthy individuals through interactions during cohabitation; however, subsequent pairing with unfamiliar naïve cohabitants may weaken this interaction effect.