Nicol M B, Hirst J J, Walker D W
Department of Physiology, Monash University, Victoria 3168, Clayton, Australia.
Neurosci Lett. 2001 Jun 22;306(1-2):13-6. doi: 10.1016/s0304-3940(01)01861-4.
This study examines the effect of inhibiting the synthesis of gamma-aminobutyric acid(A) (GABA(A)) agonist steroids on behavioural activity and somatosensory evoked potentials (SEP) in late gestation fetuses. Pregnane steroid production was suppressed by infusion of the 5alpha-reductase inhibitor, finasteride in chronically catheterised fetal sheep, 130-135 days gestation. Finasteride treatment (160 mg in 10 ml of vehicle over 2 h) significantly increased the incidence of fetal arousal during the period 4-10 h after commencing the infusion (P<0.05, n=6), whereas other behavioural parameters were not effected. In three of four animals, finasteride produced an increase in the amplitude of the N22 peak of the SEP during high voltage electrocortical activity. We conclude that suppression of pregnane steroid synthesis, by inhibition of the 5alpha-reductase enzyme, increases arousal activity in the fetus which is consistent with a reduction in GABA(A) receptor mediated inhibition.
本研究考察了抑制γ-氨基丁酸A(GABA(A))激动剂类固醇的合成对妊娠晚期胎儿行为活动和体感诱发电位(SEP)的影响。通过向妊娠130 - 135天的慢性插管胎羊输注5α-还原酶抑制剂非那雄胺来抑制孕烷类固醇的产生。非那雄胺治疗(10 ml溶媒中含160 mg,2小时内输注完毕)在开始输注后4 - 10小时期间显著增加了胎儿觉醒的发生率(P<0.05,n = 6),而其他行为参数未受影响。在四只动物中的三只,非那雄胺在高电压皮层电活动期间使SEP的N22峰振幅增加。我们得出结论,通过抑制5α-还原酶来抑制孕烷类固醇合成会增加胎儿的觉醒活动,这与GABA(A)受体介导的抑制作用减弱是一致的。