Effect of single-dose lemborexant on spontaneous locomotor activity in wild-type and orexin neuron-deficient mice

Wild-type male mice (age: 9 weeks; body weight: 19.4–22.5 g) were dosed p.o. with vehicle (5% [v/v] dimethyl sulfoxide, 10% [v/v] cremophor in 10 mmol/L HCl; 10 mL/kg; n = 16) or lemborexant (30 [n = 8] or 100 mg/kg [n = 7]) at Zeitgeber time 3:40 or 5:30. One hour after dosing, mice were placed in an open field arena (VersaMax, AccuScan Instruments, Columbus, OH) and locomotor activity was automatically recorded as infrared light beam breaks as previously described [49]. For activity values, all horizontal and vertical infrared light beam break counts were summed over 1 h after the start of locomotor activity recording.

In a separate study, orexin neuron-deficient mice (age: 18–26 weeks; body weight: 27.9–36.0 g) were dosed p.o. with vehicle (as above; n = 8) or 100 mg/kg lemborexant (n = 8), the maximum dose tested in wild-type mice, at Zeitgeber time 3:40 or 5:30. Thirty minutes later, locomotor activity was recorded and summed over 1 h as described above.