An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats
An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats
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DOI：
10.1111/j.1471-4159.2004.02991.x
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发表时间：
2005-03-01
影响因子：
4.7
通讯作者：
Hayaishi, O
中科院分区：
文献类型：
--
作者：
Hong, ZY;Huang, ZL;Hayaishi, O
腺苷A（2A）受体（A（2A）R）在睡眠过程中起着重要的调节作用。然而，A（2A）R介导睡眠的分子机制仍有待阐明。在这里，我们使用脑电图和肌电图记录结合体内微透析来研究A（2A）R激动剂CGS 21680对睡眠和脑中组胺和GABA释放的影响。在自由活动的大鼠中，将CGS 21680应用于基底前脑吻侧下方的蛛网膜下腔显著促进睡眠并抑制额叶皮质中的组胺释放。组胺释放量与非快动眼睡眠时间呈负相关（r =-0.652）。在麻醉大鼠，CGS 21680抑制组胺释放在额叶皮质和内侧视前区在剂量依赖性的方式，并增加GABA的释放，特别是在组胺能结节乳头核，但不是在额叶皮质。此外，用GABA（A）拮抗剂印防己毒素灌注结节乳头核可拮抗CGS 21680对组胺释放的抑制作用。提示A（2A）R激动剂通过增加结节乳头核GABA的释放，抑制组胺能系统，从而诱导睡眠。
The adenosine A(2A) receptor (A(2A)R) has been demonstrated to play a crucial role in the regulation of the sleep process. However, the molecular mechanism of the A(2A)R-mediated sleep remains to be elucidated. Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A(2A)R agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain. In freely moving rats, CGS21680 applied to the subarachnoid space underlying the rostral basal forebrain significantly promoted sleep and inhibited histamine release in the frontal cortex. The histamine release was negatively correlated with the amount of non-rapid eye movement sleep (r = - 0.652). In urethane-anesthetized rats, CGS21680 inhibited histamine release in both the frontal cortex and medial pre-optic area in a dose-dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. Moreover, the CGS21680-induced inhibition of histamine release was antagonized by perfusion of the tuberomammillary nucleus with a GABA(A) antagonist, picrotoxin. These results suggest that the A(2A)R agonist induced sleep by inhibiting the histaminergic system through increasing GABA release in the tuberomammillary nucleus.