Effect of dexamethasone treatment on maturational changes in the NMDA receptor in sheep brain

The objective of the present study was to examine the effect of antenatal o r postnatal treatment with corticosteroids on the NMDA receptor, one of the mediators of both normal brain development and hypoxic-ischemic injury, by determining the characteristics of the receptor MK-801 binding site in unt reated and corticosteroid-treated fetal and newborn lambs. H-3-MK-801 bindi ng was performed in cerebral cortical cell membranes from fetal sheep at 88 , 120, and 136 d gestation (term = 150 d), and from 5-d-old lambs and adult ewes. Animals were randomized to receive dexamethasone [fetuses: 6 mg, i.m . every 12 hr for four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.2 5 mg/kg (high dose) every 12 hr for four doses] or placebo. During developm ent, B-max (apparent number of receptors) increased, reaching a maximum in 5-d-old lambs (p < 0.05) and decreasing in the adult brain. K-d (dissociati on constant) did not change, suggesting that receptor affinity was not alte red during maturation. Dexamethasone treatment had no effect on MK-801 bind ing in the fetus or adult, but in lambs was associated with a significant d ecrease in B-max from 2.17 +/- 0.18 pmol/mg protein in placebo-treated anim als to 1.65 +/- 0.8 and 1.62 +/- 0.07 pmol/mg protein in low-dose and high- dose animals, respectively. Affinity for H-3-MK-801 decreased 20% after dex amethasone treatment in lambs only (p < 0.05). Thus, dexamethasone treatmen t appears to modify the NMDA receptor only during a specific period of brai n development.