Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats

Abstract

BackgroundInfectious diseases and inflammation during pregnancy increase the offspring’s risk for behavioral disorders. However, how immune stress affects neural circuitry during development is not well known. We tested whether a prenatal immune challenge interferes with the development of social play and with neural circuits implicated in social behavior.MethodsPregnant rats were given intraperitoneal injections of the bacterial endotoxin lipopolysaccharide (LPS – 100 μg /kg) or saline on the 15th day of pregnancy. Offspring were tested for social play behaviors between postnatal days 26–40. Brains were harvested on postnatal day 45 and processed for arginine vasopressin (AVP) mRNA in situ hybridization.ResultsIn males, LPS treatment reduced the frequency of juvenile play behavior and reduced AVP mRNA expression in the medial amygdala and bed nucleus of the stria terminalis. These effects were not found in females. LPS treatment did not change AVP mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, or supraoptic nucleus of either sex, nor did it affect the sex difference in the size of the sexually dimorphic nucleus of the preoptic area.ConclusionsGiven AVP’s central role in regulating social behavior, the sexually dimorphic effects of prenatal LPS treatment on male AVP mRNA expression may contribute to the sexually dimorphic effect of LPS on male social play and may, therefore, increase understanding of factors that contribute to sex differences in social psychopathology.

Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system

“…Importantly, our results show that EE can rescue the brain from the social deficits that follow MIA. In line with other inflammatory models (Kirsten et al, 2010;Taylor et al, 2012), our male ACC-LPS rats had a reduction in the percentage of time they spent in social contact. However, these animals actively engaged in affiliative behaviors at a level similar to other groups, although these interactions did not seem to be reciprocated, an effect prevented by EE.…”

“…However, these animals actively engaged in affiliative behaviors at a level similar to other groups, although these interactions did not seem to be reciprocated, an effect prevented by EE. Since the quantity and quality of social interaction is dependent on how two animals engage and respond to each other (Pellis et al, 1997;Taylor et al, 2012), our choice of using mixed-treatment (i.e., ACC-LPS/ACC-saline, EE-saline/ACC-saline) as opposed to matched (i.e., ACC-LPS/ACC-LPS, EE-saline/EE-saline) pairs may have masked additional effects of LPS.…”

Tracing the trajectory of behavioral impairments and oxidative stress in an animal model of neonatal inflammation

“…Notably, lower social engagement following MIA in the early-to-mid gestational period has been reported to occur in a sex-specific manner with males but not females being affected (Taylor et al, 2012;Connors et al, 2014). However, in SC-housed rats, we demonstrate reduced social contact in juveniles of both sexes using the dual administration nLPS model.…”

Social rejection following neonatal inflammation is mediated by olfactory scent cues

“…The anxiolytic diazepam was therefore administered to juvenile nLPS animals to determine if the social contact they received from conspecifics would increase. Given that lower levels of social interaction following early administration of LPS tend to occur in males, more so than females (Connors et al, 2014;Taylor et al, 2012), we focused our investigations on the former sex.…”