Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist
Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist
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DOI：
10.1046/j.1460-9568.1999.00569.x
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发表时间：
1999-05-01
影响因子：
3.4
通讯作者：
Hayaishi, O
中科院分区：
文献类型：
--
作者：
Satoh, S;Matsumura, H;Hayaishi, O
本研究表明，腺苷A（2A）受体选择性激动剂2-[对-（2-羧乙基）苯乙氨基]-5 '-N-乙基甲酰氨基腺苷（CGS 21680）的促睡眠效力随给药部位而变化。在大鼠活动期，通过长期植入套管连续给予CGS 21680 6 h。插管的尖端位于蛛网膜下腔或脑室中，邻近涉及睡眠-觉醒现象调节的已建立的脑区，即吻侧基底前脑、内侧视前区、外侧视前区、下丘脑后部和笔和延髓的背侧被盖。在2.0 pmol/min的输注速率下，非快速眼动睡眠的增加幅度从14 min（增加15%）变化到96 min（增加103%），快速眼动睡眠的增加幅度从6 min（增加40%）变化到28 min（增加264%）。当CGS 21680被施用到基底前脑吻侧下方的蛛网膜下腔时，两种类型的睡眠的最大增加发生。这些发现被解释为意味着主要的，如果不是唯一的，负责CGS 21680诱导睡眠的网站位于或靠近吻侧基底前脑。这一解释得到了以下发现的支持：给予CGS 21680至基底前脑的喙侧产生了Fos在丘脑核壳和嗅结节内侧部分内的主要表达，并且将CGS 21680微透析灌注到丘脑核壳中也表现出促进睡眠的作用。
The present study has demonstrated that the sleep-promoting potency of 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A(2A) receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep-wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pens and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non-rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680-inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep-promoting effect.