Fig. 4 | Scientific Reports

Fig. 4

From: TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models

Fig. 4

Effects of TAK-861, modafinil, and clomipramine on narcolepsy-like symptoms in orexin-tTA;TetO DTA mice during the active phase. (a) Time schedule of drug administration in orexin-tTA;TetO DTA mice during the active phase for evaluation for sleep/wakefulness states and cataplexy-like episodes. TAK-861, modafinil, clomipramine, or vehicle was administered orally to mice at ZT14, and then EEG/EMG and locomotor activity were recorded. Effects on wakefulness time of (b) TAK-861 (0.3 and 1 mg/kg), (c) modafinil (30 and 100 mg/kg), and (d) clomipramine (15 and 50 mg/kg) for 3 h after administration in orexin-tTA;TetO DTA mice. Blue arrows indicate the sampling time for the c-Fos mapping study in Fig. 5. Effects on cataplexy-like episodes of (e) TAK-861 (0.3 and 1 mg/kg), (f) modafinil (30 and 100 mg/kg), and (g) clomipramine (15 and 50 mg/kg) for 3 h after administration in orexin-tTA;TetO DTA mice. Mean ± standard error of the mean; n = 7–8. *p < 0.05, **p < 0.01, ***p < 0.001, compared with vehicle-treated mice, as determined by two-tailed Williams/Shirley-Williams test. DTA diphtheria toxin A, EEG electroencephalogram, EMG electromyogram.

Back to article page