GABA receptor modulation of 5-HT neuronal firing: characterization and effect of moderate in vivo variations in glucocorticoid levels
GABA receptor modulation of 5-HT neuronal firing: characterization and effect of moderate in vivo variations in glucocorticoid levels
复制标题
DOI：
10.1016/j.neuint.2004.05.003
复制
发表时间：
2004-12-01
影响因子：
4.2
通讯作者：
Gartside, SE
中科院分区：
文献类型：
--
作者：
Judge, SJ;Ingram, CD;Gartside, SE
vskip-2 pt电生理学研究表明，中缝背核（DRN）中5-HT神经元的放电可能受GABA（A）和GABA（B）受体的调节。在这里，我们解决的问题，是否个别5-HT神经元的活动是由GABA（A）和GABA（B）受体调节。此外，我们还研究了GABAA和GABA（B）受体激活的浓度-反应关系，并确定了GABA受体对5-HT神经元放电的调节是否因循环皮质酮的适度改变而改变。用体外细胞外电生理方法检测大鼠DRN内5-HT神经元的活性。GABA（A）受体激动剂4，5，6，7-四氢异恶唑并-[5，4-c]-吡啶-3-醇盐酸盐（THIP）（25 KM）和GABA（B）受体激动剂巴氯芬（1 μ M）均抑制所有测试的单个神经元的放电。对THIP（5、10、25 μ M）和巴氯芬（1、3、10 μ M）的反应是浓度依赖性的，并分别被GABA（A）和GABA（B）受体拮抗剂荷包牡丹碱（50 μ M）和法氯芬（200 μ M）减弱。为了研究皮质酮对5-HT神经元对GABA受体激活的敏感性的影响，在肾上腺切除的动物上进行了实验，在正常昼夜范围内将皮质酮维持在低或中等水平两周。皮质酮水平的这些变化对GABA（A）或GABA（B）受体激活的5-HT神经元反应没有显著影响。数据表明，GABA对5-HT神经元活性的控制是由GABA（A）和GABA（B）受体介导的，并且这种控制对循环糖皮质激素水平的适度变化不敏感。(C)2004爱思唯尔有限公司保留所有权利。
vskip-2pt Evidence from electrophysiological studies suggests that 5-HT neuronal firing in the dorsal raphe nucleus (DRN) may be regulated by both GABA(A) and GABA(B) receptors. Here, we addressed the question of whether the activity of individual 5-HT neurons is regulated by both GABA(A) and GABA(B) receptors. In addition, we examined the concentration-response relationships of GABAA and GABA(B) receptor activation and determined if GABA receptor regulation of 5-HT neuronal firing is altered by moderate alterations in circulating corticosterone. The activity of 5-HT neurons in the DRN of the rat was examined using in vitro extracellular electrophysiology. The firing of all individual neurons tested was inhibited by both the GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol hydrochloride (THIP) (25 KM) and the GABA(B) receptor agonist baclofen (1 muM). Responses to THIP (5, 10, 25 muM) and baclofen (1, 3, 10 muM) were concentration dependent and attenuated by the GABA(A) and GABA(B) receptor antagonists, bicuculline (50 muM) and phaclofen (200 muM), respectively. To examine the effects of corticosterone on the sensitivity of 5-HT neurons to GABA receptor activation, experiments were conducted on adrenalectornized animals with corticosterone maintained for two weeks at either a low or moderate level within the normal diurnal range. These changes in corticosterone levels had no significant effects on the 5-HT neuronal response to either GABA(A) or GABA(B) recepter activation. The data indicate that the control of 5-HT neuronal activity by GABA is mediated by both GABA(A) and GABA(B) receptors and that this control is insensitive to moderate changes in circulating glucocorticoid levels. (C) 2004 Elsevier Ltd. All rights reserved.