Table 1.
Selective effects of MT2 agonist UCM765 on standard sleep parameters
| Treatment group | NREM sleep latency (min) | NREM sleep total time (min) | REM sleep latency (min) | REM sleep total time (min) | Wakefulness total time (min) |
|---|---|---|---|---|---|
| A (rat) | |||||
| Vehicle (n = 7) | 24.9 ± 2.8 | 60.9 ± 3.2 | 44.4 ± 3.0 | 11.2 ± 2.0 | 107.9 ± 4.7 |
| UCM793 40 mg (n = 7) | 22.5 ± 3.6 | 55.3 ± 5.6 | 61.6 ± 15.0 | 10.9 ± 2.2 | 113.2 ± 6.4 |
| UCM793 60 mg (n = 6) | 27.6 ± 3.7 | 58.8 ± 5.7 | 57.5 ± 10.2 | 9.3 ± 1.1 | 111.9 ± 5.7 |
| UCM793 80 mg (n = 6) | 22.8 ± 30.9 | 48.3 ± 5.2 | 56.4 ± 9.2 | 8.3 ± 0.4 | 123.4 ± 5.9 |
| B (rat) | |||||
| Vehicle + vehicle (n = 6) | 31.3 ± 4.2 | 53.7 ± 4.1 | 51.8 ± 6.0 | 7.3 ± 0.5 | 119.0 ± 4.6 |
| Vehicle + UCM765 40 mg (n = 6) | 19.5 ± 2.7* | 72.6 ± 5.0*,# | 75.3 ± 11.2 | 7.8 ± 1.2 | 99.6 ± 5.8*,# |
| 4P-PDOT 10 mg + vehicle (n = 6) | 25.8 ± 3.4 | 60.5 ± 5.2 | 75.6 ± 9.0 | 8.2 ± 1.5 | 111.3 ± 6.3 |
| 4P-PDOT 10 mg + UCM765 40 mg (n = 6) | 20.7 ± 3.2 | 57.4 ± 5.7 | 65.8 ± 11.4 | 6.9 ± 0.8 | 115.7 ± 6.2 |
| C (mouse) | |||||
| WT + vehicle (n = 8) | 26.3 ± 1.9 | 64.4 ± 4.4 | 52.5 ± 6.2 | 6.4 ± 1.3 | 109.2 ± 5.7 |
| WT + UCM765 40 mg (n = 8) | 12.4 ± 1.6** | 89.3 ± 5.6*** | 71.6 ± 10.0 | 6.1 ± 1.0 | 84.6 ± 5.7*** |
| MT1 KO + vehicle (n = 6) | 38.5 ± 4.5 | 50.5 ± 3.9 | 63.3 ± 5.0 | 4.0 ± 0.5 | 125.6 ± 4.0 |
| MT1 KO + UCM765 40 mg (n = 6) | 18.0 ± 2.6*** | 66.8 ± 3.8* | 69.1 ± 11.7 | 3.5 ± 0.5 | 109.7 ± 3.0* |
| MT2 KO + vehicle (n = 6) | 27.9 ± 2.6 | 51.0 ± 4.0 | 63.8 ± 9.5 | 6.3 ± 0.8 | 122.7 ± 4.2 |
| MT2 KO + UCM765 40 mg (n = 6) | 20.0 ± 1.4 | 48.8 ± 4.1 | 65.5 ± 11.1 | 5.8 ± 1.4 | 125.4 ± 5.8 |
| D (mouse) | |||||
| MT2 KO + vehicle (n = 6) | 27.9 ± 2.6 | 51.0 ± 4.0 | 63.8 ± 9.5 | 6.3 ± 0.8 | 122.7 ± 4.2 |
| MT2 KO + DZ 2 mg (n = 4) | 10.1 ± 0.7* | 76.0 ± 2.8** | 62.1 ± 12.3 | 5.1 ± 1.0 | 98.9 ± 2.3** |
EEG/EMG recordings are from 6:00 to 9:00 P.M. (lights off at 7:30 P.M.). Data are expressed as mean ± SEM; the number of animals per group is indicated in brackets. Group A, Lack of effect of increasing doses of the nonselective MT1/MT2 agonist class congener UCM793 (40, 60, and 80 mg/kg, s.c.) in rats. Group B, Blockade of UCM765 effects by the MT2 antagonist 4P-PDOT in rats. Treatment with vehicle or UCM765 (40 mg/kg, s.c.) was administered 10 min after the pretreatment with vehicle or 4P-PDOT (10 mg/kg, s.c.). *p < 0.05, vehicle + UCM765 versus vehicle + vehicle; #p < 0.05, 4P-PDOT + UCM765 versus vehicle + UCM765, by SNK post hoc test. No differences were observed in latency and total time in REMS. Group C, Effects of UCM765 (40 mg/kg, s.c.) on sleep parameters in MT2 and MT1 receptor KO and WT mice. UCM765 decreased the latency to sleep in WT and MT1 KO, but not in MT2 KO mice. UCM765 increased NREMS total time in MT1 KO, but not in MT2 KO mice. REMS latency was not modified in MT1 KO and MT2 KO mice, and UCM765 had no effect on latency and total time in REMS. UCM765 decreased the total time of wakefulness in WT and MT1 KO, but not in MT2 KO mice. *p < 0.05; **p < 0.01; ***p < 0.001 by Fisher's PLSD test comparing vehicle versus UCM765 treatment. Group D, Diazepam (2 mg/kg, s.c.) was still active in MT2 KO mice. *p < 0.05; **p < 0.01 by Student's t test.