Characterisation of GABA(A) receptors in fetal, neonatal and adult ovine brain: region and age related changes and the effects of allopregnanolone

Progesterone metabolites acting via GABA(A) receptors suppress central nerv ous system (CNS) activity. The aim of the present study was to examine bind ing characteristics of GABA(A) receptors in fetal, newborn and adult sheep brains using [S-35]TBPS, and to determine the effects of allopregnanolone o n this binding. Receptor affinity (K-D) and density (B-MAX) in the brainste m were not different in fetal, newborn (1-2 days old) and adult brains. In the hypothalamus K-D and B-MAX increased significantly in the fetus between 85 and 128 days gestation, and were then similar to postnatal and adult va lues. In the frontal cortex k(D) and B-MAX increased progressively between 85 days and term (similar to 147 days gestation), and were then not differe nt from postnatal and adult values. The K-i values for the GABA(A) receptor antagonist picrotoxin was similar at all ages. Allopregnanolone inhibited [S-35]TBPS binding in the presence of 5 mu M GABA, but enhanced binding in the absence of GABA. These results show that (i), functional GABA(A) recept ors are present in the fetal brain from at least 85 days gestation; (ii), 3 alpha-pregnane steroids modify receptor affinity in the late gestation fet al brain; and (iii) there are region-specific changes in GABA(A) receptor b inding parameters. Steroid modulation of the GABA(A) receptor in the fetal brain is likely to influence fetal CNS activity in late gestation. (C) 2000 Elsevier Science Ltd. All rights reserved.