Influence of metyrapone treatment during pregnancy on the development and maturation of brain monoaminergic systems in the rat.
OBJECTIVE
This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains.


METHODS
Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum.


RESULTS
Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times.


CONCLUSIONS
These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones.
Leret
M L
ML
Department of Animal Physiology, Complutense University of Madrid, Spain. mlleret@bio.ucm.es
Rua
C
C
Garcia-Montojo
M
M
Lecumberri
M
M
González
J C
JC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D001923:Brain Chemistry; D003345:Corticosterone / Q000096:biosynthesis / Q000097:blood; D004298:Dopamine / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis*
D004791:Enzyme Inhibitors; D012701:Serotonin; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine; D008797:Metyrapone