Prenatal dexamethasone exposure affects anxiety-like behaviour and neuroendocrine systems in an age-dependent manner.
Prenatal stress has been reported to alter the development of the central nervous system functions. This alteration is thought to be partly caused by increased fetal exposure to glucocorticoid. To clarify how prenatal stress affects neuroendocrine systems and behaviour in an age-dependent manner, we administered a synthetic glucocorticoid, dexamethasone, as a stressor to pregnant rats at gestational days 16-21 and examined the developmental changes in behaviour, hypothalamic corticotropin-releasing factor mRNA expression, corticosterone response and glucocorticoid receptor expression in male offspring. Prenatal dexamethasone exposure decreased corticotropin-releasing factor mRNA in the hypothalamus and disturbed the plasma corticosterone response to restraint stress in the offspring at postnatal week 4 (PW4). In contrast, it was not until PW10 that increased anxiety-like behaviour emerged in the dexamethasone-exposed offspring. In association with the acquisition of increased anxiety-like behaviour at PW10, glucocorticoid receptor expression was decreased in the amygdala in dexamethasone-exposed offspring at PW7 and PW10. Thus, our longitudinal analysis suggests that prenatal exposure to glucocorticoid hampers neuroendocrinological development in the offspring during early life, and that this disturbance results in the induction of increased anxiety-like behaviour in adulthood.
Nagano
Masatoshi
M
Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Ozawa
Hitoshi
H
Suzuki
Hidenori
H
D000367:Age Factors; D000679:Amygdala / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000235:genetics / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000254:growth & development* / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods
D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone