Serotonin modulation of cell excitability and of [3H]GABA and [3H]D-aspartate efflux in primary cultures of rat cortical neurons
Serotonin modulation of cell excitability and of [3H]GABA and [3H]D-aspartate efflux in primary cultures of rat cortical neurons
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DOI：
10.1016/j.neuropharm.2006.10.017
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发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Siniscalchi, A.
中科院分区：
文献类型：
--
作者：
Bianchi, C.;Marani, L.;Siniscalchi, A.
在大鼠原代皮层神经元培养中研究了5-羟色胺（5-HT）对神经元兴奋性（以去极化诱导的放电率评估）和氨基酸释放（以电诱发的[H-3]GABA和[H-3] D-天冬氨酸外排测量）的影响。5-HT对神经元兴奋性表现出浓度依赖性的双峰效应：在3-10 μ M时，它通过5-HT 2A受体增加兴奋性，并被选择性5-HT 2A拮抗剂MDL 100907阻断，而在30-100 μ M时，它通过5-HT 1A受体降低兴奋性，反过来，5-HT浓度依赖性地抑制[H-3]GABA的外排（pEC（50）=4.74），WAY 100135可阻断这种抑制作用，GR 55562则无此作用，相反，5-HT浓度依赖性地增加刺激诱发的[H-3] D-天冬氨酸外排（pEC（50）= 4.71）。甲硫替平促进了这种增加，ICS 205930（一种选择性5-HT 3受体拮抗剂）逆转为抑制。在ICS 205930存在的情况下，5-HT诱导的抑制被选择性5-HT 1D/B受体拮抗剂GR 55562阻止，但不能被WAY 100135阻止。这些结果表明，5-HT通过5-HT 1A受体抑制GABA的释放，并对谷氨酸的释放产生双重调节，主要是易化性的（通过5-HT 3受体），但也有抑制性的（通过5-HT 1D/B受体），导致含氨基酸神经递质的神经元对兴奋性信号的预先正性调节。(c)2006爱思唯尔有限公司保留所有权利。
The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [H-3]GABA and [H-3]D-aspartate efflux, were investigated in rat primary cortical neuronal cultures.5-HT displayed a concentration-dependent, bimodal effect on neuronal excitability: at 3-10 mu M it increased excitability through 5-HT2A receptors, and was blocked by the selective 5-HT2A antagonist MDL 100907, whereas at 30-100 mu M it reduced excitability through 5-HT1A receptors, and was, in turn, blocked by the selective 5-HT1A antagonist WAY 100135.The electrically-evoked [H-3]GABA efflux was concentration-dependently inhibited by 5-HT (pEC(50)=4.74) and such inhibition was prevented by WAY 100135, but not by GR 55562, a selective 5-HT1D/B receptor antagonist.Conversely, 5-HT concentration-dependently increased stimulus-evoked [H-3]D-aspartate efflux (pEC(50) = 4.71). The increase was facilitated by methiothepin and was reversed into inhibition by ICS 205930, a selective 5-HT3 receptor antagonist. In the presence of ICS 205930, the inhibition induced by 5-HT was prevented by the selective 5-HT1D/B receptor antagonist GR 55562, but not by WAY 100135.]These findings suggest that 5-HT inhibits GABA release through 5-HT1A receptors and exerts a dual modulation on glutamate release, mostly facilitatory (through 5-HT3 receptors) but also inhibitory (through 5-HT1D/B receptors), leading to a prevalently positive modulation of the excitatory signal by amino acid neurotransmitter containing neurons. (c) 2006 Elsevier Ltd. All rights reserved.