Role of adenosine A(1) receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats.
Role of adenosine A(1) receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats.
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DOI：
10.1016/j.brainres.2009.09.066
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发表时间：
2009-12-22
期刊：
影响因子：
2.9
通讯作者：
McGinty D
中科院分区：
文献类型：
--
作者：
Alam MN;Kumar S;Rai S;Methippara M;Szymusiak R;McGinty D
下丘脑周围外侧区（PF-LHA）与觉醒的调节有关。PF-LHA包含在非REM睡眠期间静止的唤醒活性神经元，并且在表达肽下丘脑泌素（HCRT）的神经元的情况下，在非REM和REM睡眠期间都静止。腺苷是一种内源性睡眠因子，最近的证据表明腺苷通过A1受体作用于PF-LHA神经元以促进睡眠。我们研究了双侧激活以及阻断PF-LHA中A1受体对自由行为大鼠睡眠-觉醒的影响。在人工脑脊液（aCSF）和腺苷A1受体拮抗剂1，3-二丙基-8-苯基黄嘌呤（CPDX; 5μM和50μM）或A1受体激动剂N6-环戊基腺苷（CPA; 5 μ M和50 μM）反向微透析灌注PF-LHA 2 h后，记录雄性Wistar大鼠的睡眠-觉醒曲线。在开灯阶段将CPDX灌注到PF-LHA中产生唤醒（F=7.035，p <0.001），并伴随着减少非REM（F=7.295，p<0.001）和REM睡眠（F=3.456，p<0.004）。相比之下，在熄灯期向PF-LHA灌注CPA显著抑制觉醒（F = 7.891; p <0.001），增加非REM（F = 8.18; p <0.001）和REM睡眠（F = 30.036; p = <0.001）。这些结果表明，PF-LHA是腺苷通过A1受体作用于PF-LHA神经元以促进睡眠的位点之一。
The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of arousal. The PF-LHA contains wake-active neurons that are quiescent during nonREM sleep and in the case of neurons expressing the peptide hypocretin (HCRT), quiescent during both nonREM and REM sleep. Adenosine is an endogenous sleep factor and recent evidence suggests that adenosine via A1 receptors may act on PF-LHA neurons to promote sleep. We examined the effects of bilateral activation as well as blockade of A1 receptors in the PF-LHA on sleep-wakefulness in freely behaving rats. The sleep-wake profiles of male Wistar rats were recorded during reverse microdialysis perfusion of artificial cerebrospinal fluid (aCSF) and two doses of adenosine A1 receptor antagonist, 1,3-dipropyl-8-phenylxanthine (CPDX; 5μM and 50μM) or A1 receptor agonist, N6-cyclopentyladenosine (CPA; 5μM and 50μM) into the PF-LHA for 2h followed by 4h of aCSF perfusion. CPDX perfused into the PF-LHA during lights-on phase produced arousal (F=7.035, p <0.001) and concomitantly decreased both nonREM (F=7.295, p<0.001) and REM sleep (F=3.456, p<0.004). In contrast, CPA perfused into the PF-LHA during lights-off phase significantly suppressed arousal (F = 7.891; p <0.001) and increased nonREM (F = 8.18; p <0.001) and REM sleep (F = 30.036; p = <0.001). These results suggest that PF-LHA is one of the sites where adenosine, acting via A1 receptors, inhibits PF-LHA neurons to promote sleep.
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