Prenatal Dexamethasone Impairs Behavior and the Activation of the BDNF Exon IV Promoter in the Paraventricular Nucleus in Adult Offspring

Prenatal manipulations to the hypothalamic-pituitary-adrenal axis are shown to affect auditory responses to an acoustic challenge as well as behavior in adult life. To achieve these results, we examined the effect of prenatal dexamethasone (DEX) treatment in male and female adult rat offspring by assessing body and adrenal weight, anxiety using the elevated plus maze (EPM), and acoustic startle responses as well as the effects of acoustic challenge in the paraventricular nucleus (PVN). DEX male offspring had reduced adrenal gland weight in adult life and demonstrated anxiolytic-like behavior when tested on the EPM. The acoustic startle amplitude in naive DEX-treated male offspring was significantly higher compared with saline (SAL)-treated males and females and DEX-treated females. When challenged with either a glucocorticoid agonist or antagonist, the startle response of the SAL-treated males and females significantly increased or decreased in the presence of agonist and antagonist treatment, respectively, whereas DEX males and females were not affected. Acoustic challenge caused an increase in c-fos mRNA and glucocorticoid receptor nuclear translocation in the PVN of all groups. BDNF and TrkB mRNA increased in the PVN after acoustic challenge in the SAL-treated males and females but not in the DEX males or females. These findings exemplify the differential sensitivity of the developing nervous and endocrine systems to prenatal hormonal stress and demonstrate that prenatal DEX treatment elicits long-term behavioral alterations related to anxiety and auditory processing. ( Endocrinology 149: 6356-6365, 2008)