Neurosteroid modulation of GABA(A) receptors in the developing rat brain cortex

The allosteric modulation of GABA(A) receptors in the rat brain cortex by neurosteroids was studied at different developmental stages. GABA(A) receptors were identified using [³H]muscimol binding to membrane preparations obtained from embryos and neonates (postnatal day 0-PN0; postnatal day 5-PN5). Data analysis disclosed a unique population of binding sites at all ages tested. An increase in the number of receptors was observed during development reaching almost adult levels at PN5. The neurosteroids pregnanolone and allopregnanolone failed to modulate [³H]muscimol specific binding in embryos and neonates, but a positive modulation was obtained in 5-day old animals. The addition of 1 μM pregnanolone induced a 3-6-fold increase [³H]muscimol affinity in PN5 (n = 3; P < 0.03), and a 2-fold increase in receptors number in adults (n = 3; P < 0.03). The differences observed in allosteric modulation during development suggest that a change occurred during the first week of life, and this change might affect GABA(A) receptor function.