Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Department of Neuroscience and Experimental Therapeutics, Texas A&M University System, College Station, TX, USA.
Br J Anaesth. 2021 Sep;127(3):435-446. doi: 10.1016/j.bja.2021.03.029. Epub 2021 May 8.
We recently showed that a neurosteroid analogue, (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rats. The aim of the present study was to evaluate the hypnotic and anaesthetic potential of 3β-OH further using electroencephalography.
We used behavioural assessment and cortical electroencephalogram (EEG) spectral power analysis to examine hypnotic and anaesthetic effects of 3β-OH (30 and 60 mg kg) administered intraperitoneally or intravenously to young adult male and female rats.
We found dose-dependent sex differences in 3β-OH-induced hypnosis and EEG changes. Both male and female rats responded similarly to i.p. 3β-OH 30 mg kg. However, at the higher dose (60 mg kg, i.p.), female rats had two-fold longer duration of spontaneous immobility than male rats (203.4 [61.6] min vs 101.3 [32.1] min), and their EEG was suppressed in the low-frequency range (2-6 Hz), in contrast to male rats. Although a sex-dependent hypnotic effect was not confirmed after 30 mg kg i.v., female rats appeared more sensitive to 3β-OH with relatively small changes within delta (1-4 Hz) and alpha (8-13 Hz) bands. Finally, 3β-OH had a rapid onset of action and potent hypnotic/anaesthetic effect after 60 mg kg i.v. in rats of both sexes; however, all female rats and only half of the male rats reached burst suppression, an EEG pattern usually associated with profound inhibition of thalamocortical networks.
Based on its behavioural effects and EEG signature, 3β-OH is a potent hypnotic in rats, with female rats being more sensitive than male rats.
我们最近发现一种神经甾体类似物，（3β,5β,17β）-3-羟基雄烷-17-腈（3β-OH），可诱导大鼠催眠。本研究旨在进一步使用脑电图评估 3β-OH 的催眠和麻醉潜力。
我们使用行为评估和皮质脑电图（EEG）频谱功率分析来检查 3β-OH（30 和 60 mg/kg）腹膜内或静脉注射对年轻成年雄性和雌性大鼠的催眠和麻醉作用。
我们发现 3β-OH 诱导的催眠和 EEG 变化存在剂量依赖性的性别差异。雄性和雌性大鼠对腹膜内 3β-OH 30 mg/kg 的反应相似。然而，在较高剂量（60 mg/kg，腹膜内）时，雌性大鼠的自发不动时间是雄性大鼠的两倍长（203.4[61.6]min 比 101.3[32.1]min），并且它们的 EEG 在低频范围（2-6 Hz）被抑制，而雄性大鼠则没有。虽然静脉内 30 mg/kg 时未确认性别依赖性催眠作用，但雌性大鼠对 3β-OH 更敏感，其 delta（1-4 Hz）和 alpha（8-13 Hz）频段内的变化相对较小。最后，3β-OH 在雄性和雌性大鼠中静脉内 60 mg/kg 后具有快速的作用起始和有效的催眠/麻醉作用；然而，所有雌性大鼠和只有一半的雄性大鼠达到爆发抑制，这是一种通常与丘脑皮质网络深度抑制相关的 EEG 模式。
根据其行为效应和 EEG 特征，3β-OH 是大鼠的一种有效的催眠药，雌性大鼠比雄性大鼠更敏感。
