Synergistic sedative effects of noradrenergic α1- and β-receptor blockade on forebrain electroencephalographic and behavioral indices
Synergistic sedative effects of noradrenergic α1- and β-receptor blockade on forebrain electroencephalographic and behavioral indices
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DOI：
10.1016/s0306-4522(00)00215-3
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
España, RA
中科院分区：
文献类型：
--
作者：
Berridge, CW;España, RA
蓝斑-去甲肾上腺素能系统对前脑神经元和行为活动状态产生激活影响。例如，在麻醉的大鼠中，单侧蓝斑刺激激发双侧前脑脑电图活动。用去甲肾上腺素能β-拮抗剂预处理阻断这种作用，表明β-受体在前脑蓝斑依赖性激活中起关键作用。与此相一致的是，刺激位于某些基底前脑结构中的β受体会在未麻醉的大鼠中引起持续的警觉觉醒。为了评估α 1和β受体对维持行为和前脑激活的作用程度，我们在未麻醉大鼠中检测了α 1、β和α 1/β受体联合阻断对脑电图和行为的影响，大鼠单独或与不同剂量的α（1）-拮抗剂哌唑嗪（腹腔内）和/或β-拮抗剂噻吗洛尔（脑室内）联合给药。给药后30分钟，将动物置于轻度唤醒的新环境中，先前已证明该环境可引起中枢去甲肾上腺素能系统的激活，并在溶剂处理对照中持续唤醒。记录行为和脑电活动，然后进行评分。用功率谱分析法分析脑电图活动，观察到：（1）单独β受体阻滞剂不改变清醒时的行为或脑电图指标;（2）单独α 1受体阻滞剂增加皮层脑电图活动中的高电压纺锤体活动，而这种活动与行为活动减少有关;（iii）联合α（1）-和β-受体阻滞剂可显著增加慢波活动（0.33-2.0Hz），也与行为活动减少有关。所有这些效应都依赖于给药剂量和测试开始后的时间，这些结果表明，α（1）和β受体的联合作用对皮层神经元活动模式产生了独特的协同作用，而皮层神经元活动模式是警觉觉醒的基本要素。(C)2000 IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
The locus coerulcus-noradrenergic system exerts an activating influence on forebrain neuronal and behavioral activity states. For example, in the anesthetized rat, unilateral locus coeruleus stimulation elicits bilateral activation of forebrain electroencephalographic activity. Pretreatment with a noradrenergic beta-antagonist blocks this effect, suggesting that beta-receptors play a critical role in locus coeruleus-dependent activation of the forebrain. Consistent with this, stimulation of beta-receptors located in certain basal forebrain structures evokes sustained periods of alert waking in the unanesthetized rat. Similar forebrain and behavioral activating effects are observed with alpha(1)-receptor stimulation within these basal forebrain regions.To assess the extent to which alpha(1)- and beta-receptors contribute to the maintenance of behavioral and forebrain activation, we examined the electroencephalographic and behavioral effects of alpha(1)-, beta- and combined alpha(1)/beta-receptor blockade in the unanesthetized rat, Rats were treated individually or in combination with either varying doses of the alpha(1)-antagonist, prazosin (intraperitoneally), and/or the beta-antagonist, timolol (intracerebroventricularly). Thirty minutes following treatment, animals were placed in a mildly-arousing novel environment, which has been demonstrated previously to elicit activation of central noradrenergic systems and sustained waking in vehicle-treated controls. Behavior and electroencephalographic activity were recorded and later scored. Electroencephalographic activity was analysed using power spectrum analysis.The following were observed: (i) beta-receptor blockade alone does not alter behavioral or electroencephalographic indices of alert waking; (ii) alpha(1)-receptor blockade alone increases high-voltage spindle activity in cortical electroencephalographic activity that was associated with decreased behavioral activity; (iii) combined alpha(1)- and beta-receptor blockade elicits a substantial increase in slow-wave activity (0.33-2.0Hz), also in association with decreased behavioral activity. All of these effects were dependent on the dose administered and time following initiation of testing.These results indicate that the combined actions of alpha(1)- and beta-receptors exert distinct and synergistic actions on cortical neuronal activity patterns that are essential elements of alert waking. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.