PROGRAMMING OF BRAIN-STEM SEROTONIN TRANSPORTER DEVELOPMENT BY PRENATAL GLUCOCORTICOIDS

Prenatal stress or exposure to excess glucocorticoids are known to alt er central nervous system function and to result in lasting changes in reactions to stress. The potential involvement of specific elements o f brainstem serotonergic neurons was examined in the current study. Pr egnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gest ational days 17, 18 and 19, and the effects on development of the sero tonin presynaptic transporter were assessed from birth to young adulth ood by measurement of [H-3]paroxetine binding to membrane preparations . Dexamethasone produced a dose-dependent retardation of body and brai nstem growth but evoked a significant elevation of [H-3]paroxetine bin ding that persisted into adulthood. Effects on [H-3]paroxetine binding were robust even at the lowest dose, which did not suppress growth, i ndicating that the programming of this transporter is more sensitive t o glucocorticoids than is general development. At the highest dose, pr omotional effects on serotonin transporter expression were offset by i mpaired growth, so that the peak effect was seen at the intermediate d ose of dexamethasone. There were no comparable effects on serotonin tr ansmitter levels, indicating selectivity toward promotion of transport er expression as distinct from simply increasing the number of seroton ergic nerve terminals or all nerve terminal components. As the effect of prenatal dexamethasone treatment on the serotonin transporter is mo re persistent than those on other monoamine transporters, and is not s hared by postnatal treatment or by treatment in adulthood, it likely r epresents specific programming by glucocorticoids during the prenatal period. Aberrant serotonergic transporter expression may contribute to alterations of synaptic function that ultimately produce the physiolo gical abnormalities seen after prenatal stress or glucocorticoid treat ment.