Dexmedetomidine reduces long-term potentiation in mouse hippocampus
Dexmedetomidine reduces long-term potentiation in mouse hippocampus
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DOI：
10.1097/01.anes.0000296076.04510.e1
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发表时间：
2008-01-01
期刊：
影响因子：
8.8
通讯作者：
Sekiguchi, Masayuki
中科院分区：
文献类型：
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作者：
Takamatsu, Isao;Iwase, Ayano;Sekiguchi, Masayuki
背景：右美托咪定（precdex; Abbott Laboratories, Abbott Park， IL）是一种选择性α 2-肾上腺素能激动剂，对咪唑啉受体也有亲和力。在临床研究中，右美托咪定具有镇静作用和损害记忆的作用，但右美托咪定对大脑突触可塑性的作用尚不明确。在本研究中，作者研究了右美托咪定对小鼠海马CA1区两种形式的突触可塑性-长期增强（LTP）和配对脉冲促进的影响。方法：记录小鼠海马CA1辐射层Schaffer侧侧诱发场兴奋性突触后电位。用场兴奋性突触后电位上升相的斜率来估计突触传递的强度。结果：右美托咪定在“theta burst”刺激前应用20 min，以剂量依赖性减弱LTP，右美托咪定的半抑制浓度为28.6 +/- 5.7 nM。右美托咪定对LTP的抑制作用并没有被α 2-肾上腺素受体拮抗剂（育亨宾）、咪唑啉I型受体和α 2-肾上腺素受体拮抗剂（依法罗森）、α 1-肾上腺素受体拮抗剂（吡唑嗪）或α -氨基丁酸a型受体拮抗剂（微毒素）所消除。然而，咪唑啉2型受体和a2肾上腺素受体拮抗剂（咪唑嗪）完全阻断右美雷利定诱导的衰减。此外，选择性咪唑啉2型受体配体2-苯并呋喃酰-2-咪唑啉降低了LTP。另一种咪唑啉2型受体配体2-（4,5-二氢咪唑-2-基）-喹啉可以消除2-苯并呋喃酰-2-咪唑啉引起的衰减，但2-（4,5-二氢咪唑-2-基）-喹啉不能消除右美托咪定对UP的抑制作用。右美托咪定不影响配对脉冲促进。结论：右美托咪定通过咪唑啉2型受体和α 2肾上腺素受体影响小鼠海马CA1区LTP的表达。
Background: Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective alpha 2-adrenergic agonist that also has affinity for imidazoline receptors. in clinical studies, dexmedetomidine has sedative effects and impairs memory, but the action of dexmedetomidine on synaptic plasticity in the brain has yet to be established. in the present study, the authors investigated the effects of dexmedetomidine on two forms of synaptic plasticity-long-term potentiation (LTP) and paired-pulse facilitation-in the CA1 region of mouse hippocampal slices.Methods: The authors recorded Schaffer collateral-evoked field excitatory postsynaptic potentials from mouse hippocampal slices in CA1 stratum radiatum. The slope of the rising phase of the field excitatory postsynaptic potential was used to estimate the strength of synaptic transmission.Results: Application of dexmedetomidine for 20 min before "theta burst" stimulation dose-dependently attenuated LTP, and half-inhibitory concentration of dexmedetomidine was 28.6 +/- 5.7 nM. The inhibitory effect of dexmedetomidine on LTP was not abolished by an alpha 2-adrenoceptor antagonist (yohimbine), an imidazoline type I receptor and a2-adrenoceptor antagonist (efaroxan), an alpha 1-adrenoceptor antagonist (prazosin), or a,gamma-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and a2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetonlidine-induced attenuation. Furthermore, 2-benzofuranyl-2-imidaloline, a selective imidazoline type 2 receptor ligand, reduced LTP. 2-(4,5-dihydroimidaz-2-yl)-quinoline, another imidazoline type 2 receptor ligand, abolished the 2-benzofuranyl-2-imidaloline-induced attenuation, but the inhibitory effect of dexmedetomidine on UP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation.Conclusion: Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha 2-adrenoceptors.