Takamatsu Isao, Iwase Ayano, Ozaki Makoto, Kazama Tomiei, Wada Keiji, Sekiguchi Masayuki
Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan.
Anesthesiology. 2008 Jan;108(1):94-102. doi: 10.1097/01.anes.0000296076.04510.e1.
Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective alpha2-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.
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.
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 alpha2-adrenoceptor antagonist (yohimbine), an imidazoline type 1 receptor and alpha2-adrenoceptor antagonist (efaroxan), an alpha1-adrenoceptor antagonist (prazosin), or a gamma-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and alpha2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetomidine-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 LTP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation.
Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha2-adrenoceptors.
右美托咪定（Precedex；雅培实验室，伊利诺伊州雅培公园）是一种选择性α2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并损害记忆，但右美托咪定对大脑突触可塑性的作用尚未明确。在本研究中，作者研究了右美托咪定对小鼠海马切片CA1区两种突触可塑性形式——长时程增强（LTP）和双脉冲易化的影响。
作者记录了小鼠海马切片CA1辐射层中Schaffer侧支诱发的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。
在“theta爆发”刺激前应用右美托咪定20分钟，可剂量依赖性地减弱LTP，右美托咪定的半数抑制浓度为28.6±5.7 nM。右美托咪定对LTP的抑制作用不能被α2肾上腺素能拮抗剂（育亨宾）、咪唑啉1型受体和α2肾上腺素能拮抗剂（依酚氯铵）、α1肾上腺素能拮抗剂（哌唑嗪）或γ-氨基丁酸A型受体拮抗剂（印防己毒素）消除。然而，咪唑啉2型受体和α2肾上腺素能拮抗剂（伊达唑胺）可完全阻断右美托咪定诱导的减弱作用。此外，选择性咪唑啉2型受体配体2-苯并呋喃基-2-咪唑啉可降低LTP。另一种咪唑啉2型受体配体2-（4,5-二氢咪唑-2-基）喹啉可消除2-苯并呋喃基-2-咪唑啉诱导的减弱作用，但右美托咪定对LTP的抑制作用不能被2-（4,5-二氢咪唑-2-基）喹啉消除。右美托咪定不影响双脉冲易化。
右美托咪定通过咪唑啉2型受体和α2肾上腺素能受体损害小鼠海马CA1区的LTP。
