PRENATAL STRESS IMPAIRS LEARNING AND MEMORY PERFORMANCE IN RATS IN A SEX-DEPENDENT MANNER: ROLE FOR THE MEDIAL PREFRONTAL CORTEX?

Maternal exposure to social stress in late pregnancy results in enhanced hypothalamo-pituitary-adrenal (HPA) axis responses to stress in the adult prenatally stressed (PNS) offspring. PNS may also impair later cognitive function. Although the neural mechanisms are not known, reprogramming of the HPA axis has been proposed. The medial prefrontal cortex (mPFC) plays an important role in cognition and also contributes to the glucocorticoid negative feedback control of the HPA axis via glucocorticoid receptors (GR). Using a spatial memory task (Barne?s maze) we tested whether learning is impaired in PNS male and female offspring under basal and acute stress conditions. Under basal conditions, spatial learning was not different between control and PNS rats in either sex. 30min restraint impaired learning in PNS males, but not females. In situ hybridisation revealed that basal expression of GR and its transcription factor, nerve growth factor inducible gene-A mRNA was significantly reduced in the mPFC in both male and female PNS rats compared with controls. We hypothesised that impaired prelimbic cortex-mediated glucocorticoid feedback control of the HPA axis may underlie the learning deficits in PNS rats under stressful conditions, thus bilateral ibotenic acid lesions were made in the prelimbic cortex 7d before Barnes maze testing. Acute stress impaired learning in both sham and lesioned rats, however the lesion had no further effect. In conclusion, spatial learning is impaired in PNS males under acute stress conditions, however altered prelimbic cortex-mediated glucocorticoid negative feedback control of the HPA axis does not seem to underlie these stress-induced deficits.