Development of a mild prenatal stress rat model to study long term effects on neural function and survival

Early development of the brain's neural circuitry has been shown to be vulnerable to high levels of circulating steroid hormones such as corticosterone. These steroid hormones are lipophylic and can cross the placental barrier especially during the last week of gestation leading to disturbances in the formation of neural circuits that contain amongst others dopaminergic and serotonergic neurons. The effects of this disruption of neuronal circuit formation during gestation has been shown to manifest in adult offspring as behavioural abnormalities such as anxiety and an abnormal hypothalamic-pituitary-adrenal (HPA) axis. Models of prenatal stress include food deprivation and a model that involves exposure of the pregnant rats to different stressors, commonly referred to as a mild stress model. The objective of this study was to create a mild stress model that did not manifest as anxiety in adult offspring. In the last week of gestation, the pregnant dams were divided into three groups; (1) non-stressed (2) 50% food-deprived and (3) mildly stressed rats that we will refer to as the mildly stressed rats. Following birth, all pups were cross-fostered onto non-stressed dams and on postnatal day 60 (P60), behaviour in the elevated plus maze and the open field box was tested. On P66 the rats were exposed to an acute restraint stress following which trunk blood was collected for HPA axis analysis. The adrenal glands were also dissected and weighed. Results show that the mildly stressed rat model of prenatal stress is even milder than models described in the literature, since we did not find differences in time spent in the open arms of the elevated plus maze or adrenal gland size. In the open field, our model displayed slightly less locomotor activity and also had a slightly blunted adrenocorticotropic hormone (ACTH) response to restraint stress even though the corticosterone response was similar to controls.