Figure 1.

γ-Aminobutyric acid (GABA_A) modulators and dual orexin receptor antagonist (DORAs) dose-responsively increase sleep time in active-phase dosing (zeitgeber time (ZT)17). Average time (min±standard error of mean (SEM)) male Sprague–Dawley rats (n=16 per study) spent in sleep/wake state compared with vehicle treatment for respective low, mid, and high (eszopiclone: 3, 6, and 10 mg/kg; zolpidem: 10, 30, and 60 mg/kg; DORA-22: 3, 10, and 30 mg/kg) oral (per os) doses during 3-day crossover design studies during active phase. Each treatment dose was conducted independently and compared with within-subject vehicle. Statistics were calculated within each study using two-way analysis of variance (ANOVA) with repeated measure (factors for treatment and day); *P<0.05, **P<0.01.