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 3alpha-hydroxy pregnane steroids are active at GABA(A) receptors in fetal sheep and can modulate sleep/wake activity before birth.
Department of Physiology, Monash University, Clayton, Victoria, Australia. marcus.nicol@med.monash.edu.au
M B
MB
Nicol
J J
JJ
Hirst
D W
DW
Walker
D000818:Animals; D002404:Catheterization; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects* / Q000502:physiology; D005333:Fetus; D007262:Infusions, Intravenous; D007536:Isomerism; D010296:Parietal Lobe / Q000502:physiology; D011278:Pregnanes / Q000008:administration & dosage / Q000494:pharmacology*; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D012756:Sheep; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
D011278:Pregnanes; D011963:Receptors, GABA-A; D011280:Pregnanolone