Dexamethasone treatment in utero enhances neonatal cholinergic nerve terminal development in rat brain.
Fetal glucocorticoid administration has been proposed to elicit both promotional and inhibitory effects on neuronal development. In the current study, pregnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19, and the effects on development of central cholinergic projections was assessed on postnatal day 1 by measuring the specific binding of [3H]hemicholinium-3 to the high affinity choline transporter localized in cholinergic nerve terminal membranes. Dexamethasone produced a dose-dependent retardation of brain region growth, but enhanced [3H]hemicholinium-3 binding in both the forebrain and the midbrain + brainstem. At the highest dose, the promotional effect on [3H]hemicholinium-3 binding was lost in the forebrain, a region that is particularly sensitive during late gestation to inhibitory effects of glucocorticoids on neuronal development. These results indicate that, even in the face of growth retardation, glucocorticoids promote the development of central cholinergic projections; however, at high doses, inhibitory actions of the steroid can offset the promotional effects in some regions.
Zahalka
E A
EA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001921:Brain / Q000187:drug effects*; D002799:Cholinergic Fibers / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006426:Hemicholinium 3 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D006426:Hemicholinium 3; D003907:Dexamethasone