NORADRENERGIC CONTROL OF THALAMIC OSCILLATION - THE ROLE OF ALPHA-2 RECEPTORS
NORADRENERGIC CONTROL OF THALAMIC OSCILLATION - THE ROLE OF ALPHA-2 RECEPTORS
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DOI：
10.1111/j.1460-9568.1991.tb00083.x
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发表时间：
1991-03-01
影响因子：
3.4
通讯作者：
ZIEGLER, M
中科院分区：
文献类型：
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作者：
BUZSAKI, G;KENNEDY, B;ZIEGLER, M
在自由活动的大鼠上研究了α-肾上腺素能药物对反映丘脑振荡的新皮层高电压峰电位和波梭（HVS）的影响。 清醒但不动的动物自发发生HVS。 α-1拮抗剂、哌唑嗪和α-2激动剂、甲苯噻嗪和可乐定的外周给药以剂量依赖性方式增加HVS的发生率和持续时间。 α-2受体拮抗剂育亨宾和三环类抗抑郁药地昔帕明和阿米替林显著降低了新皮质HVS的发生率。 双侧微量注射α-2受体激动剂到丘脑腹外侧核区，但不进入海马或胼胝体，是有效的外周注射这些药物。 赛拉嗪在显示高HVS自发率的Fischer 344大鼠中最有效，而在Sprague -道利和布法罗品系中效果较差。 预先丘脑内注射α-2受体拮抗剂育亨宾可拮抗可乐定的HVS促进作用。 皮摩尔量的可乐定单侧注射的HVS的幅度增加。 脑池内或丘脑内注射6-羟基多巴胺（但外周注射DSP-4不会）对丘脑去甲肾上腺素能传入神经造成神经毒性破坏，从而增加了HVS的发生率。 重要的是，丘脑内给予甲苯噻嗪在破坏丘脑去甲肾上腺素能末梢后继续诱导HVS。 阿米替林长期给药（3周）下调α-2肾上腺素受体后，HVS的发生率降低，丘脑内甲苯噻嗪诱导HVS的有效性显著降低。 基于这些发现，我们认为α-2肾上腺素能药物对丘脑振荡的主要作用可能是由位于丘脑皮质神经元上的突触后α-2肾上腺素能受体介导的。 我们假设丘脑中的去甲肾上腺素对中继细胞具有双重作用：分别通过α-1和α-2受体阻断和促进丘脑振荡。 最终的生理效应被认为是这些肾上腺素能受体亚型的相对密度和亲和力的函数。
The effects of alpha-adrenergic drugs on neocortical high voltage spike and wave spindles (HVS), reflecting thalamic oscillation, was investigated in freely moving rats. HVS occurred spontaneously in the awake but immobile animal. Peripheral administration of the alpha-1 antagonist, prazosin and alpha-2 agonists, xylazine and clonidine increased the incidence and duration of HVS in a dose-dependent manner. The alpha-2 antagonist, yohimbine and the tricyclic antidepressants, desipramine and amitriptyline, significantly decreased the incidence of the neocortical HVS. Bilateral microinjections of the alpha-2 agonists into the nucleus ventralis lateralis area of the thalamus, but not into the hippocampus or corpus callosum, was as effective as peripheral injection of these drugs. Xylazine was most effective in Fischer 344 rats that display high spontaneous rate of HVS and less effective in the Sprague - Dawley and Buffalo strains. The HVS-promoting effect of clonidine was antagonized by prior intrathalamic injection of the alpha-2 antagonist, yohimbine. The amplitude of the HVS was increased by picomole amounts of unilaterally-injected clonidine. Neurotoxic destruction of the thalamopetal noradrenergic afferents by intracisternal or intrathalamic injection of 6-hydroxydopamine, but not by peripheral administration of DSP-4, increased the incidence of HVS. Importantly, intrathalamic administration of xylazine continued to induce HVS after destroying the thalamic noradrenergic terminals. Following downregulation of the alpha-2 adrenoceptors by chronic administration (3 weeks) of amitriptylene the incidence of HVS decreased and the effectiveness of intrathalamic xylazine on the induction of HVS was significantly reduced. Based on these findings, we suggest that a major action of alpha-2 adrenergic drugs on thalamic oscillation may be mediated by postsynaptic alpha-2 adrenoceptors located on the thalamocortical neurons. We hypothesize that noradrenaline in the thalamus has a dual effect on the relay cells: blocking and promoting thalamic oscillation via alpha-1 and alpha-2 receptors, respectively. The final physiological effect is assumed to be a function of the relative density and affinity of these adrenergic receptor subtypes.