In vivo electrophysiological evidence for tonic activation by endogenous noradrenaline of α2-adrenoceptors on 5-hydroxytryptamine terminals in the rat hippocampus
In vivo electrophysiological evidence for tonic activation by endogenous noradrenaline of α2-adrenoceptors on 5-hydroxytryptamine terminals in the rat hippocampus
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大鼠海马 5-羟色胺末端 α2-肾上腺素受体内源性去甲肾上腺素强直激活的体内电生理证据
DOI：
10.1007/bf00167444
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
C. Montigny
中科院分区：
文献类型：
--
作者：
R. Mongeau;P. Blier;C. Montigny
通过比较静脉注射去甲肾上腺素能药物前后电刺激5-HT上行通路抑制CA 3背侧海马锥体神经元放电活动的有效性，研究了α2肾上腺素能异源受体的激活。地昔帕明（2 mg/kg），一种选择性去甲肾上腺素再摄取阻滞剂，降低了刺激的效力;这种作用被α2-肾上腺素受体拮抗剂育亨宾（0.5 mg/kg）和（-）米安色林（0.5 mg/kg）逆转，但不能被咪唑克生（0.5 mg/kg）逆转，咪唑克生是一种对咪唑啉识别位点具有优先亲和力的肾上腺素受体拮抗剂。低剂量可乐定（2和10 μg/kg）可增强刺激效应，高剂量可乐定（100和400 μg/kg）可减弱刺激效应，而0.1和1 mg/kg育亨宾可分别逆转可乐定的这种增强和减弱效应。用去甲肾上腺素神经毒素6-羟多巴胺预处理大鼠，可消除低剂量可乐定（10 μg/kg）的增强作用。然而，高剂量可乐定（100 μg/kg）的抑制作用并没有被这种预处理改变。这些结果表明，低剂量可乐定优先激活去甲肾上腺素能神经元上的α2肾上腺素能自身受体，从而减弱内源性去甲肾上腺素对5-HT神经传递的紧张性抑制作用，而高剂量可乐定则通过直接激活5-HT终末上的α2肾上腺素能异源受体而减少5-HT神经传递。此外，选择性α2-肾上腺素能异源受体拮抗剂（-）米安色林（0.5 mg/kg）本身可增加5-HT神经传递的效力，而育亨宾和咪唑克生未观察到这种作用。这些结果提示，在体内，内源性去甲肾上腺素可紧张性激活大鼠海马5-HT终末α2-肾上腺素能受体，调节5-HT的释放。
SummaryThe activation of α2-adrenergic heteroreceptors was studied by comparing the effectiveness of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons prior to, and following, the intravenous administration of noradrenergic agents. Desipramine (2 mg/kg), a selective noradrenaline reuptake blocker, reduced the efficacy of the stimulation; this effect was reversed by the α2-adrenoceptor antagonists yohimbine (0.5 mg/kg) and (-)mianserin (0.5 mg/kg), but not by idazoxan (0.5 mg/kg), an adrenoceptor antagonist with preferential affinity for the imidazoline recognition sites. Low doses of the α2-adrenoceptor agonist clonidine (2 and 10 μg/kg) enhanced the efficacy of the stimulation, while high doses (100 and 400 μg/kg) reduced it. These incremental and decremental effects of clonidine were reversed by 0.1 and 1 mg/kg of yohimbine, respectively. The enhancing effect of the low dose of clonidine (10 μg/kg) was abolished in rats pretreated with the noradrenaline neurotoxin 6-hydroxydopamine. However, the inhibitory effect of a high dose of clonidine (100 μg/kg) was unaltered by this pretreatment. These results indicate that low doses of clonidine preferentially activate α2-adrenergic autoreceptors on the noradrenaline neurons resulting in a reduction of the tonic inhibitory effect of endogenous noradrenaline on 5-HT neurotransmission, while higher doses of clonidine would decrease 5-HT neurotransmission through the direct activation of α2-adrenergic heteroreceptors on 5-HT terminals. Furthermore, the selective α2-adrenergic heteroreceptors antagonist(-)mianserin (0.5 mg/kg) increased by itself the efficacy of 5-HT neurotransmission, an effect not observed with yohimbine and idazoxan. Taken together, these results suggest that, in vivo, the α2-adrenoceptors on 5-HT terminals of the rat hippocampus are tonically activated by endogenous noradrenaline and modulate 5-HT release.
非肾上腺素能[3H]咪唑克生结合位点在物理上与α2-肾上腺素能受体不同。
影响因子：
3.6
作者：
Michel,MC;Regan,JW;Gerhardt,MA;Neubig,RR;Insel,PA;Motulsky,HJ
通讯作者：
Motulsky,HJ