Glucocorticoids and the development of neuronal function: effects of prenatal dexamethasone exposure on central noradrenergic activity.
Although glucocorticoids slow the development of most cell types, they have been hypothesized to promote the differentiation of catecholaminergic cells. In the current study, pregnant rats were given dexamethasone on gestational days 17, 18 and 19, and the functional state of noradrenergic synaptic activity was assessed throughout postnatal development by measurements of transmitter levels and turnover, and receptor binding capabilities. Despite growth inhibition caused by dexamethasone, the steroid treatment had little or no effect on transmitter levels or receptor binding and accelerated the maturation of norepinephrine turnover in a regionally selective manner. Effects were most notable in the midbrain and brainstem, where turnover rose to maximum levels 1-2 weeks in advance of controls. Turnover also leveled off prematurely in the dexamethasone group, leading to deficits in the postweaning period and into young adulthood. Although similar patterns were obtained in other, later-developing regions, the effects were less consistent and robust; the smaller effects also extended to dopamine turnover. These results suggest that glucocorticoids have a specific promotional effect on the development of central catecholaminergic activity and that administration of exogenous steroids during critical periods of development can lead to lasting functional abnormalities.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Lappi
S E
SE
McCook
E C
EC
Tayyeb
M I
MI
Eylers
J P
JP
Seidler
F J
FJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001933:Brain Stem / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D002395:Catecholamines / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008636:Mesencephalon / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000032:analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016548:Prosencephalon / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D011941:Receptors, Adrenergic / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D002395:Catecholamines; D005938:Glucocorticoids; D011941:Receptors, Adrenergic; D003907:Dexamethasone; D004298:Dopamine; D009638:Norepinephrine