Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109-5615, USA.
Sleep. 2013 Mar 1;36(3):337-43. doi: 10.5665/sleep.2444.
Gamma-aminobutyric acid (GABA) causes phasic inhibition via synaptic GABAA receptors and tonic inhibition via extrasynaptic GABAA receptors. GABA levels in the extracellular space regulate arousal state and cognition by volume transmission via extrasynaptic GABAA receptors. GABAergic transmission in the pontine reticular formation promotes wakefulness. No previous studies have determined whether an agonist at extrasynaptic GABAA receptors administered into the pontine reticular formation alters sleep and wakefulness. Therefore, this study used gaboxadol (THIP; agonist at extrasynaptic GABAA receptors that contain a δ subunit) to test the hypothesis that extrasynaptic GABAA receptors within the pontine reticular formation modulate sleep and wakefulness.
Within/between subjects.
University of Michigan.
Adult male Crl:CD*(SD) (Sprague-Dawley) rats (n = 10).
Microinjection of gaboxadol, the nonsubtype selective GABAA receptor agonist muscimol (positive control), and saline (negative control) into the rostral pontine reticular formation.
Gaboxadol significantly increased wakefulness and decreased both nonrapid eye movement sleep and rapid eye movement sleep in a concentration-dependent manner. Relative to saline, gaboxadol did not alter electroencephalogram power. Microinjection of muscimol into the pontine reticular formation of the same rats that received gaboxadol increased wakefulness and decreased sleep.
Tonic inhibition via extrasynaptic GABAA receptors that contain a δ subunit may be one mechanism by which the extracellular pool of endogenous GABA in the rostral pontine reticular formation promotes wakefulness.
Vanini G; Baghdoyan HA. Extrasynaptic GABAA receptors in rat pontine reticular formation increase wakefulness. SLEEP 2013;36(3):337-343.
γ-氨基丁酸（GABA）通过突触 GABAA 受体引起相性抑制，通过细胞外 GABAA 受体引起紧张性抑制。细胞外间隙中的 GABA 水平通过细胞外 GABAA 受体通过容积传递来调节觉醒状态和认知。桥脑网状结构中的 GABA 能传递促进觉醒。以前没有研究确定是否在桥脑网状结构中给予细胞外 GABAA 受体激动剂会改变睡眠和觉醒。因此，本研究使用gaboxadol（THIP；细胞外 GABAA 受体激动剂，含有 δ 亚基）来检验 extrasynaptic GABAA 受体在桥脑网状结构中调节睡眠和觉醒的假说。
在/在受试者之间。
密歇根大学。
成年雄性 Crl：CD*（SD）（Sprague-Dawley）大鼠（n = 10）。
gaboxadol、非亚型选择性 GABAA 受体激动剂 muscimol（阳性对照）和盐水（阴性对照）微注射到桥脑网状结构的头端。
gaboxadol 以浓度依赖性方式显著增加觉醒并减少非快速眼动睡眠和快速眼动睡眠。与盐水相比，gaboxadol 不会改变脑电图功率。向接受 gaboxadol 的相同大鼠的桥脑网状结构中注射 muscimol 会增加觉醒并减少睡眠。
含有 δ 亚基的细胞外 GABA 库通过细胞外 GABAA 受体的紧张性抑制可能是桥脑网状结构中促进觉醒的机制之一。
Vanini G；Baghdoyan HA。大鼠桥脑网状结构中的细胞外 GABAA 受体增加觉醒。睡眠 2013；36(3):337-343。
