Table 1.
DORAs, selective OX2R antagonist MK1064, and typical hypnotic Zolpidem significantly increased the amount of NREM sleep within 6 hours following the injections (unit: minute)
| Test | Sleep/wake state | Optogenetic stimulation-evoked wakefulness | NOR | |||
|---|---|---|---|---|---|---|
| Group | Wakefulness (minute) | NREM sleep (minute) | REM sleep (minute) | Latency (s) | Bout length (s) | Novel time (%) |
| Vehicle | 195.997 ± 9.915 | 155.621 ± 8.939 | 8.198 ± 1.454 | 0.201 ± 0.012 | 81.53 ± 18.00 | 45.660 ± 4.252 |
| DORA12 | 135.444 ± 21.109* | 217.724 ± 21.098** | 9.487 ± 0.572 | 0.231 ± 0.017 | 11.76 ± 0.4826**** | 67.140 ± 4.153* |
| MK6096 | 87.079 ± 7.458**** | 270.212 ± 8.000**** | 3.290 ± 1.426* | 0.234 ± 0.006 | 12.69 ± 0.6572**** | 74.160 ± 6.643** |
| 1SORA1 | 222.313 ± 9.603 | 130.188 ± 8.908 | 7.420 ± 1.258 | 0.221 ± 0.007 | 96.18 ± 13.44 | 48.033 ± 8.124 |
| MK1064 | 56.152 ± 3.316**** | 303.848 ± 3.316**** | 0# | 0.264 ± 0.010 | 14.272 ± 0.596**** | 60.834 ± 7.091 |
| Zolpidem | 95.708 ± 4.904**** | 263.082 ± 4.714**** | 0.866 ± 0.532**** | 0.234 ± 0.013 | 15.680 ± 0.639**** | 71.352 ± 18.468 |
Dual antagonism of OX1/2Rs and selective antagonism of OX2R as well as Zolpidem decreased the duration of optogenetic stimulation-evoked wakefulness (unit: s). DORAs ameliorated the memory deficits by optogenetic stimulation-induced sleep fragmentation (optogenetic stimulations: 15 ms blue light pulse, at 10 Hz for 10 s; linear-mixed effects model followed by Tukey’s multiple comparisons, *p < 0.05, **p < 0.01, ****p < 0.001, #p < 0.0001; n = 6 for the panels sleep/wakefulness state and optogenetic stimulation-evoked wakefulness, n = 5 for NOR; Vehicle (solvent): 50% 0.9% Sodium Chloride, 50% PEG400; DORA12: 20 mg/kg; MK6096: 20 mg/kg; 1SORA1: 20 mg/kg; MK1064: 20 mg/kg; Zolpidem: 20 mg/kg).