Effect of microdialysis perfusion of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol in the perifornical hypothalamus on sleep-wakefulness: role of delta-subunit containing extrasynaptic GABAA receptors.
Effect of microdialysis perfusion of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol in the perifornical hypothalamus on sleep-wakefulness: role of delta-subunit containing extrasynaptic GABAA receptors.
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下丘脑周围 4,5,6,7-四氢异恶唑并-[5,4-c]吡啶-3-醇微透析灌注对睡眠-觉醒的影响：含有突触外 GABAA 受体的 δ 亚基的作用。
DOI：
10.1016/j.neuroscience.2008.02.053
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发表时间：
2008
期刊：
影响因子：
3.3
通讯作者：
McCarley,RW
中科院分区：
文献类型：
--
作者：
Thakkar,MM;Winston,S;McCarley,RW
Gaboxadol or 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP) is a selective agonist for the δ-subunit containing extrasynaptic GABAA receptors that will soon enter the U.S. market as a sleep aid (Winsky-Sommerer et al., 2007). Numerous studies have shown that systemic administration of THIP reduces wakefulness and increases sleep both in humans and rats (Lancel and Langebartels, 2000; Walsh et al., 2007). However, it is yet unclear where in the brain THIP acts to promote sleep. Since the perifornical lateral hypothalamus (PFH) contains orexin neurons and orexin neurons are critical for maintenance of arousal (McCarley, 2007), we hypothesized that THIP may act on PFH neurons to promote sleep. To test our hypothesis, we used reverse microdialysis to perfuse THIP unilaterally into the PFH and studied its effects on sleep-wakefulness during the light period in freely behaving rats. Microdialysis perfusion of THIP (100 µM) into the PFH produced a significant reduction in wakefulness with a concomitant increase in nonREM sleep as compared to ACSF perfusion. REM sleep was unaffected. This is the first study implicating the δ-subunit containing extrasynaptic GABAA receptors in PFH in control of sleep-wakefulness in freely behaving rats.
