Dubrovsky B, Filipini D, Gijsbers K, Birmingham M K
Laboratory of Neurophysiology, McGill University, Montreal, Quebec, Canada.
Ciba Found Symp. 1990;153:240-57; discussion 257-60. doi: 10.1002/9780470513989.ch14.
Steroids have fast and probably partly GABA-mediated central anaesthetic effects for which a strict structure-function correlation is required. They also affect short- and long-term activity in the CNS in other ways. One of these is long-term potentiation (the persistent facilitation of synaptic transmission), which occurs particularly in the hippocampus after repetitive stimulation of a fibre pathway. Two clearly distinguished components of the evoked response can be studied in the hippocampus: the excitatory postsynaptic potential (EPSP) which denotes the graded depolarization of the somadendritic region of the neuron and the population spike (PS), a manifestation of the all-or-none discharge of the cell action potential. Corticosterone had a significant depressant effect on the EPSP component of the evoked response immediately and 15 min after injection. Thereafter EPSP amplitudes were within normal values. Corticosterone significantly decreased the PS immediately after the train, the component remaining low 30 min after the train. 5 alpha-Dihydrocorticosterone (a ring A-reduced metabolite of corticosterone) significantly reduced the PS component of the response at all times after injection. 18-Hydroxydeoxycorticosterone and deoxycorticosterone significantly decreased both EPSP and PS components of the evoked response from the time of infusion. Contrary to expectation, tetrahydrodeoxycorticosterone was ineffective in decreasing, and if anything, enhanced the development of long-term potentiation. 18-Hydroxydeoxycorticosterone 21-acetate behaved like vehicle, except for the first 30 min after injection, when the EPSP was decreased. Different steroids can selectively affect different parts of a neuron and appear to show a different structure-function correlation for long-term potentiation from that required for anaesthesia.
类固醇具有快速且可能部分由γ-氨基丁酸介导的中枢麻醉作用,对此需要严格的结构-功能相关性。它们还以其他方式影响中枢神经系统的短期和长期活动。其中之一是长期增强作用(突触传递的持续易化),其尤其在纤维通路受到重复刺激后于海马体中发生。在海马体中可以研究诱发反应的两个明显不同的成分:兴奋性突触后电位(EPSP),它表示神经元体树突区域的分级去极化,以及群体峰电位(PS),它是细胞动作电位全或无放电的一种表现。皮质酮在注射后立即和15分钟时对诱发反应的EPSP成分具有显著的抑制作用。此后EPSP幅度在正常值范围内。皮质酮在串刺激后立即显著降低PS,该成分在串刺激后30分钟仍保持较低水平。5α-二氢皮质酮(皮质酮的A环还原代谢产物)在注射后的所有时间均显著降低反应的PS成分。18-羟基脱氧皮质酮和脱氧皮质酮从输注时起就显著降低诱发反应的EPSP和PS成分。与预期相反,四氢脱氧皮质酮在降低方面无效,而且如果有任何作用的话,是增强了长期增强作用的发展。18-羟基脱氧皮质酮21-乙酸酯的表现与溶剂相似,除了注射后的前30分钟,此时EPSP降低。不同的类固醇可以选择性地影响神经元的不同部分,并且对于长期增强作用似乎显示出与麻醉所需的结构-功能相关性不同。