Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: Possible implications for behaviour

Glucocorticoids may underlie the association between low birth weight and a dult disorders such as hyperten sion, type 2 diabetes and affective dysfunc tion. We investigated the behavioural and molecular consequences of two par adigms of prenatal dexamethasone administration in rats. Rats received dexa methasone (100 mug/kg per day) throughout pregnancy (DEX 1 -3), in the last third of pregnancy only (DEX3) or vehicle. Both dexamethasone treatments r educed birth weight. only DEX1-3 offspring had reduced body weight in adult hood. In adult offspring, both prenatal dexamethasone paradigms reduced exp loratory behaviour in an open held. In contrast, only DEX3 reduced explorat ion in an elevated plus-maze and impaired behavioural responses and learnin g in a forced-swim test. This behavioural inhibition mag. reflect increased baseline corticotrophin-releasing hormone mRNA levels (30% higher) in the central nucleus of the amygdala in both dexamethasone-exposed groups. Adult DEX3 offspring also showed increased corticotrophin-releasing hormone mRNA with unaltered glucocorticoid receptor mRNA in the hypothalamic paraventri cular nucleus and reduced hippocampal glucocorticoid- and mineralocorticoid receptor mRNA expression, suggesting reduced hippocampal sensitivity to gl ucocorticoid suppression of the stress axis. In contrast, DEX1-3 rats had n o changers in hippocampal corticosteroid receptors. but showed increased mR NA levels for both receptors in the basolateral nucleus of the amygdala. From this data we suggest that prenatal glucocorticoid exposure programs be havioural inhibition perhaps, via increased amygdalar corticotrophin-releas ing hormone levels, while DEX3 also impairs coping and learning in aversive situations. possibly via altered hippocampal corticosteroid receptor level s, Overexposure to glucocorticoids, especially late in gestation, may expla in the link between reduced early growth and adult affective dysfunction. ( C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.