Ye Jiang H, Sokol Kimberly A, Bhavsar Urvi
The Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Alcohol Clin Exp Res. 2009 Jun;33(6):1069-74. doi: 10.1111/j.1530-0277.2009.00928.x. Epub 2009 Mar 23.
Glycine is a major inhibitory neurotransmitter in the adult central nervous system (CNS), and its receptors (GlyRs) are well known for their effects in the spinal cord and the lower brainstem. Accumulating evidence indicates that GlyRs are more widely distributed in the CNS, including many supraspinal regions. Previous in vitro studies have demonstrated that ethanol potentiates the function of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been well explored.
Experiments were conducted in rats. The loss of righting reflex (LORR) was used as a marker of the hypnotic state. We compared the LORR induced by systematic administration of ethanol and of ketamine in the absence and presence of the selective glycine receptor antagonist strychnine. Ketamine is a general anesthetic that does not affect GlyRs.
Systemically administered (by intraperitoneal injection) ethanol and ketamine dose-dependently induced LORR in rats. Furthermore, systemically administered (by subcutaneous injection) strychnine dose-dependently reduced the percentage of rats exhibiting LORR induced by ethanol, increased the onset time, and decreased the duration of LORR. Strychnine had no effect, however, on the LORR induced by ketamine.
Given that hypnosis is caused by neuronal depression in upper brain areas, we therefore conclude that brain GlyRs contribute at least in part to the hypnosis induced by ethanol.
甘氨酸是成年中枢神经系统(CNS)中的一种主要抑制性神经递质,其受体(甘氨酸受体,GlyRs)因其在脊髓和低位脑干中的作用而广为人知。越来越多的证据表明,甘氨酸受体在中枢神经系统中分布更为广泛,包括许多脊髓上区域。以往的体外研究表明,乙醇可增强这些脑甘氨酸受体的功能,但脑甘氨酸受体的行为作用尚未得到充分研究。
在大鼠身上进行实验。翻正反射消失(LORR)被用作催眠状态的标志。我们比较了在有无选择性甘氨酸受体拮抗剂士的宁的情况下,系统性给予乙醇和氯胺酮所诱导的翻正反射消失情况。氯胺酮是一种不影响甘氨酸受体的全身麻醉剂。
系统性给予(腹腔注射)乙醇和氯胺酮可使大鼠剂量依赖性地出现翻正反射消失。此外,系统性给予(皮下注射)士的宁可剂量依赖性地降低乙醇诱导出现翻正反射消失的大鼠百分比,延长起效时间,并缩短翻正反射消失的持续时间。然而,士的宁对氯胺酮诱导的翻正反射消失无影响。
鉴于催眠是由大脑上部区域的神经元抑制引起 的,因此我们得出结论,脑甘氨酸受体至少部分促成了乙醇诱导的催眠作用。