Effect of pregnane steroids on electrocortical activity and somatosensory evoked potentials in fetal sheep

The effect of infusing the neuroactive steroids pregnanolone and iso- pregnanolone on somatosensory evoked potentials (SEP) and electrocortical (ECoG) activity was studied in unanaesthetised fetal sheep, 130-135 days gestation. Intravenous infusion of pregnanolone (6 mg/kg per h) significantly increased the proportion of high voltage ECoG (56.1 ± 4.8% vs. control 43.5 ± 3.2% P < 0.05), and decreased low voltage ECoG (43.9 ± 4.8% vs. control 56.6 ± 3.2%, P < 0.05). Pregnanolone treatment decreased the amplitude of the N25 peak of the SEP (89.9 ± 2.8% of control, P < 0.05) evoked following stimulation of the skin of the upper lip. In contrast, iso-pregnanolone treatment had no effect on ECoG activities, or on the amplitude and latency of peaks in the SEP. We conclude that 3α-hydroxy pregnane steroids are active at GABA(A) receptors in fetal sheep and can modulate sleep/wake activity before birth.