Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition.
Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition.
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微量胺相关受体 1 调节清醒状态和脑电图频谱组成。
DOI：
10.1038/npp.2016.216
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Kilduff,ThomasS
中科院分区：
文献类型：
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作者：
Schwartz,MichaelD;Black,SarahW;Fisher,SimonP;Palmerston,JeremiahB;Morairty,StephenR;Hoener,MariusC;Kilduff,ThomasS
痕量胺相关受体1（TAAR 1）激动剂已被证明具有促认知、抗精神病样、抗焦虑、减肥、降糖和促醒活性。我们使用Taar 1敲除（KO）和过表达（OE）小鼠和TAAR 1激动剂来阐明TAAR 1在睡眠/觉醒中的作用。记录Taar 1 KO、OE和WT小鼠的EEG、EMG、体温（T B）和自发活动（LMA）。在24小时记录以表征基础睡眠/觉醒参数后，将小鼠剥夺睡眠（SD）6小时。在另一个实验中，给予小鼠三个剂量的TAAR 1部分激动剂R 05263397、咖啡因或载体po。与WT小鼠相比，OE小鼠的基线觉醒适度增加。在NREM和REM睡眠中，KO小鼠的基线θ（4.5-9 Hz）和低γ（30-60 Hz）活性高于OE小鼠。SD后，KO和OE小鼠均表现出稳态睡眠反弹。在WT小鼠中，RO 5263397增加了觉醒，减少了NREM和REM睡眠，降低了觉醒和NREM期间的γ功率，降低了T B，但不影响LMA;这些效应在KO小鼠中不存在，在OE小鼠中增强。与此相反，咖啡因增加觉醒时间，NREM γ功率，和LMA在所有菌株与车辆相比，这种效果在KO和增强OE小鼠减弱。TAAR 1过表达适度增加觉醒，而TAAR 1部分激动增加觉醒，也减少NREM和REM睡眠。这些结果表明TAAR 1在睡眠/觉醒和皮质活动中的调节作用，并表明TAAR 1作为促进觉醒治疗的新靶点。
Trace amine-associated receptor 1 (TAAR1) agonists have been shown to have procognitive, antipsychotic-like, anxiolytic, weight-reducing, glucose-lowering, and wake-promoting activities. We used Taar1 knockout (KO) and overexpressing (OE) mice and TAAR1 agonists to elucidate the role of TAAR1 in sleep/wake. EEG, EMG, body temperature (T b), and locomotor activity (LMA) were recorded in Taar1 KO, OE, and WT mice. Following a 24 h recording to characterize basal sleep/wake parameters, mice were sleep deprived (SD) for 6 h. In another experiment, mice were given three doses of the TAAR1 partial agonist RO5263397, caffeine, or vehicle po Baseline wakefulness was modestly increased in OE compared with WT mice. Baseline theta (4.5–9 Hz) and low gamma (30–60 Hz) activity was elevated in KO compared with OE mice in NREM and REM sleep. Following SD, both KO and OE mice exhibited a homeostatic sleep rebound. In WT mice, RO5263397 increased waking and reduced NREM and REM sleep, decreased gamma power during wake and NREM, and decreased T b without affecting LMA; these effects were absent in KO mice and potentiated in OE mice. In contrast, caffeine increased wake time, NREM gamma power, and LMA in all strains compared with vehicle; this effect was attenuated in KO and potentiated in OE mice. TAAR1 overexpression modestly increases wakefulness, whereas TAAR1 partial agonism increases wakefulness and also reduces NREM and also REM sleep. These results indicate a modulatory role for TAAR1 in sleep/wake and cortical activity and suggest TAAR1 as a novel target for wake-promoting therapeutics.