, p < 0.001), and main effects of both treatment (F(4, 74.15) = 6.34, p < 0.001) and photoperiod (F(1, 179.88) = 132.73, p < 0.001). High and moderate dose JZL increased NREM bout duration across the LP (t(91.06) ! 2.94, p 0.016). The moderate dose of JZL increased NREM bout duration across the first 6 Hr of the LP (ZT00-06: t(225.33) ! 2.59, p 0.041), while high dose JZL only increased NREM bout duration later in the LP (ZT06-09: t(225.33) = 3.12, p = 0.008). The number of NREM bouts was not affected when JZL was administered before the LP. In contrast to the modest effects of JZL on REM sleep when the drug was given before the DP, administration of JZL before the LP produced a marked reduction in REM sleep (Fig 6C; bottom row). For the percent of time spent in REM sleep, there was an overall interaction (treatment x time of day within photoperiod, F(24, 224.83) = 1.61, p = 0.040), secondary interaction (treatment x photoperiod, F(4, 116.88) = 13.58, p < 0.001), nested interaction (time of day within photoperiod, F(6, 212.50) = 9.60, p < 0.001), and main effects of both treatment (FPLOS ONE | DOI:10.1371/journal.pone.0152473 March 31,17 /Endocannabinoid Signaling Regulates Sleep Stability(4, 61.32) = 7.17, p < 0.001) and photoperiod (F(1, 200.12) = 10.77, p = 0.001). Both moderate and high dose JZL reduced REM sleep time across the LP (t(77.11) -4.81, p < 0.001). Specifically, REM sleep was diminished across most time points in the LP following administration of both doses (moderate dose, ZT00-09: t(184.07) -2.81, p 0.022; high dose, ZT00-12: t (184.05) -3.87, p 0.001). For REM bout duration, there was an overall interaction (treatment x time of day within photoperiod, F(24, 192.48) = 2.02, p = 0.005), secondary interaction (treatment x photoperiod, F(4, 113.74) = 6.52, p < 0.001), and main effects of both treatment (F(4, 70.319) = 11.95, p < 0.001) and photoperiod (F(1, 165.44) = 15.90, p < 0.001). REM bout duration was suppressed by both moderate and high dose JZL across the LP (t(85.623) -27.46, p 0.001). Specifically, the moderate dose of JZL reduced REM bout duration during the first 6 Hr of the LP (ZT00-06: t(217.98) -3.27, p 0.005) and increased REM bout duration during the middle of the DP (ZT18-21: t(217.49) = 2.75, p = 0.026). High dose JZL reduced REM bout duration across the entire LP and into the first 3 Hr of the DP (ZT00-15: t(214.55) -3.21, p 0.006). For the number of REM bouts, there was a secondary interaction (treatment x photoperiod, F(4, 119.91) = 10.01, fpsyg.2017.00209 p < 0.001), nested interaction (time of day within photoperiod, F(6, 206.20) = 11.17, p < 0.001), and main effects of both treatment (F(4, 74.09) = 3.14, p = 0.019) and photoperiod (F(1, 177.54) = 27.29, p < 0.001). Again, moderate and high dose JZL reduced the number of REM bouts across the LP (t(90.894) -3.41, p 0.002). The number of REM bouts was reduced at multiple time points during the LP following JZL administration (moderate dose, ZT03-06: t(227.24) = 3.19, p < 0.001); high dose, ZT00-09: t(227.24) -2.85, p 0.019). Thus, REM sleep is markedly suppressed by acute augmentation of 2-AG tone, but only when this drug is administered immediately before the time of SART.S23503 day when mice engage in most of their REM sleep. EEG Power Spectral RG7800 supplier Quizartinib web Measurements. Given the effects of increased 2-AG signaling on NREM and REM sleep described above, we examined the spectral content of the EEG signal from the experiment where JZL was administered before the DP (Fig 7). Similar BLU-554 site BLU-554 web results., p < 0.001), and main effects of both treatment (F(4, 74.15) = 6.34, p < 0.001) and photoperiod (F(1, 179.88) = 132.73, p < 0.001). High and moderate dose JZL increased NREM bout duration across the LP (t(91.06) ! 2.94, p 0.016). The moderate dose of JZL increased NREM bout duration across the first 6 Hr of the LP (ZT00-06: t(225.33) ! 2.59, p 0.041), while high dose JZL only increased NREM bout duration later in the LP (ZT06-09: t(225.33) = 3.12, p = 0.008). The number of NREM bouts was not affected when JZL was administered before the LP. In contrast to the modest effects of JZL on REM sleep when the drug was given before the DP, administration of JZL before the LP produced a marked reduction in REM sleep (Fig 6C; bottom row). For the percent of time spent in REM sleep, there was an overall interaction (treatment x time of day within photoperiod, F(24, 224.83) = 1.61, p = 0.040), secondary interaction (treatment x photoperiod, F(4, 116.88) = 13.58, p < 0.001), nested interaction (time of day within photoperiod, F(6, 212.50) = 9.60, p < 0.001), and main effects of both treatment (FPLOS ONE | DOI:10.1371/journal.pone.0152473 March 31,17 /Endocannabinoid Signaling Regulates Sleep Stability(4, 61.32) = 7.17, p < 0.001) and photoperiod (F(1, 200.12) = 10.77, p = 0.001). Both moderate and high dose JZL reduced REM sleep time across the LP (t(77.11) -4.81, p < 0.001). Specifically, REM sleep was diminished across most time points in the LP following administration of both doses (moderate dose, ZT00-09: t(184.07) -2.81, p 0.022; high dose, ZT00-12: t (184.05) -3.87, p 0.001). For REM bout duration, there was an overall interaction (treatment x time of day within photoperiod, F(24, 192.48) = 2.02, p = 0.005), secondary interaction (treatment x photoperiod, F(4, 113.74) = 6.52, p < 0.001), and main effects of both treatment (F(4, 70.319) = 11.95, p < 0.001) and photoperiod (F(1, 165.44) = 15.90, p < 0.001). REM bout duration was suppressed by both moderate and high dose JZL across the LP (t(85.623) -27.46, p 0.001). Specifically, the moderate dose of JZL reduced REM bout duration during the first 6 Hr of the LP (ZT00-06: t(217.98) -3.27, p 0.005) and increased REM bout duration during the middle of the DP (ZT18-21: t(217.49) = 2.75, p = 0.026). High dose JZL reduced REM bout duration across the entire LP and into the first 3 Hr of the DP (ZT00-15: t(214.55) -3.21, p 0.006). For the number of REM bouts, there was a secondary interaction (treatment x photoperiod, F(4, 119.91) = 10.01, fpsyg.2017.00209 p < 0.001), nested interaction (time of day within photoperiod, F(6, 206.20) = 11.17, p < 0.001), and main effects of both treatment (F(4, 74.09) = 3.14, p = 0.019) and photoperiod (F(1, 177.54) = 27.29, p < 0.001). Again, moderate and high dose JZL reduced the number of REM bouts across the LP (t(90.894) -3.41, p 0.002). The number of REM bouts was reduced at multiple time points during the LP following JZL administration (moderate dose, ZT03-06: t(227.24) = 3.19, p < 0.001); high dose, ZT00-09: t(227.24) -2.85, p 0.019). Thus, REM sleep is markedly suppressed by acute augmentation of 2-AG tone, but only when this drug is administered immediately before the time of SART.S23503 day when mice engage in most of their REM sleep. EEG Power Spectral Measurements. Given the effects of increased 2-AG signaling on NREM and REM sleep described above, we examined the spectral content of the EEG signal from the experiment where JZL was administered before the DP (Fig 7). Similar results., p < 0.001), and main effects of both treatment (F(4, 74.15) = 6.34, p < 0.001) and photoperiod (F(1, 179.88) = 132.73, p < 0.001). High and moderate dose JZL increased NREM bout duration across the LP (t(91.06) ! 2.94, p 0.016). The moderate dose of JZL increased NREM bout duration across the first 6 Hr of the LP (ZT00-06: t(225.33) ! 2.59, p 0.041), while high dose JZL only increased NREM bout duration later in the LP (ZT06-09: t(225.33) = 3.12, p = 0.008). The number of NREM bouts was not affected when JZL was administered before the LP. In contrast to the modest effects of JZL on REM sleep when the drug was given before the DP, administration of JZL before the LP produced a marked reduction in REM sleep (Fig 6C; bottom row). For the percent of time spent in REM sleep, there was an overall interaction (treatment x time of day within photoperiod, F(24, 224.83) = 1.61, p = 0.040), secondary interaction (treatment x photoperiod, F(4, 116.88) = 13.58, p < 0.001), nested interaction (time of day within photoperiod, F(6, 212.50) = 9.60, p < 0.001), and main effects of both treatment (FPLOS ONE | DOI:10.1371/journal.pone.0152473 March 31,17 /Endocannabinoid Signaling Regulates Sleep Stability(4, 61.32) = 7.17, p < 0.001) and photoperiod (F(1, 200.12) = 10.77, p = 0.001). Both moderate and high dose JZL reduced REM sleep time across the LP (t(77.11) -4.81, p < 0.001). Specifically, REM sleep was diminished across most time points in the LP following administration of both doses (moderate dose, ZT00-09: t(184.07) -2.81, p 0.022; high dose, ZT00-12: t (184.05) -3.87, p 0.001). For REM bout duration, there was an overall interaction (treatment x time of day within photoperiod, F(24, 192.48) = 2.02, p = 0.005), secondary interaction (treatment x photoperiod, F(4, 113.74) = 6.52, p < 0.001), and main effects of both treatment (F(4, 70.319) = 11.95, p < 0.001) and photoperiod (F(1, 165.44) = 15.90, p < 0.001). REM bout duration was suppressed by both moderate and high dose JZL across the LP (t(85.623) -27.46, p 0.001). Specifically, the moderate dose of JZL reduced REM bout duration during the first 6 Hr of the LP (ZT00-06: t(217.98) -3.27, p 0.005) and increased REM bout duration during the middle of the DP (ZT18-21: t(217.49) = 2.75, p = 0.026). High dose JZL reduced REM bout duration across the entire LP and into the first 3 Hr of the DP (ZT00-15: t(214.55) -3.21, p 0.006). For the number of REM bouts, there was a secondary interaction (treatment x photoperiod, F(4, 119.91) = 10.01, fpsyg.2017.00209 p < 0.001), nested interaction (time of day within photoperiod, F(6, 206.20) = 11.17, p < 0.001), and main effects of both treatment (F(4, 74.09) = 3.14, p = 0.019) and photoperiod (F(1, 177.54) = 27.29, p < 0.001). Again, moderate and high dose JZL reduced the number of REM bouts across the LP (t(90.894) -3.41, p 0.002). The number of REM bouts was reduced at multiple time points during the LP following JZL administration (moderate dose, ZT03-06: t(227.24) = 3.19, p < 0.001); high dose, ZT00-09: t(227.24) -2.85, p 0.019). Thus, REM sleep is markedly suppressed by acute augmentation of 2-AG tone, but only when this drug is administered immediately before the time of SART.S23503 day when mice engage in most of their REM sleep. EEG Power Spectral Measurements. Given the effects of increased 2-AG signaling on NREM and REM sleep described above, we examined the spectral content of the EEG signal from the experiment where JZL was administered before the DP (Fig 7). Similar results., p < 0.001), and main effects of both treatment (F(4, 74.15) = 6.34, p < 0.001) and photoperiod (F(1, 179.88) = 132.73, p < 0.001). High and moderate dose JZL increased NREM bout duration across the LP (t(91.06) ! 2.94, p 0.016). The moderate dose of JZL increased NREM bout duration across the first 6 Hr of the LP (ZT00-06: t(225.33) ! 2.59, p 0.041), while high dose JZL only increased NREM bout duration later in the LP (ZT06-09: t(225.33) = 3.12, p = 0.008). The number of NREM bouts was not affected when JZL was administered before the LP. In contrast to the modest effects of JZL on REM sleep when the drug was given before the DP, administration of JZL before the LP produced a marked reduction in REM sleep (Fig 6C; bottom row). For the percent of time spent in REM sleep, there was an overall interaction (treatment x time of day within photoperiod, F(24, 224.83) = 1.61, p = 0.040), secondary interaction (treatment x photoperiod, F(4, 116.88) = 13.58, p < 0.001), nested interaction (time of day within photoperiod, F(6, 212.50) = 9.60, p < 0.001), and main effects of both treatment (FPLOS ONE | DOI:10.1371/journal.pone.0152473 March 31,17 /Endocannabinoid Signaling Regulates Sleep Stability(4, 61.32) = 7.17, p < 0.001) and photoperiod (F(1, 200.12) = 10.77, p = 0.001). Both moderate and high dose JZL reduced REM sleep time across the LP (t(77.11) -4.81, p < 0.001). Specifically, REM sleep was diminished across most time points in the LP following administration of both doses (moderate dose, ZT00-09: t(184.07) -2.81, p 0.022; high dose, ZT00-12: t (184.05) -3.87, p 0.001). For REM bout duration, there was an overall interaction (treatment x time of day within photoperiod, F(24, 192.48) = 2.02, p = 0.005), secondary interaction (treatment x photoperiod, F(4, 113.74) = 6.52, p < 0.001), and main effects of both treatment (F(4, 70.319) = 11.95, p < 0.001) and photoperiod (F(1, 165.44) = 15.90, p < 0.001). REM bout duration was suppressed by both moderate and high dose JZL across the LP (t(85.623) -27.46, p 0.001). Specifically, the moderate dose of JZL reduced REM bout duration during the first 6 Hr of the LP (ZT00-06: t(217.98) -3.27, p 0.005) and increased REM bout duration during the middle of the DP (ZT18-21: t(217.49) = 2.75, p = 0.026). High dose JZL reduced REM bout duration across the entire LP and into the first 3 Hr of the DP (ZT00-15: t(214.55) -3.21, p 0.006). For the number of REM bouts, there was a secondary interaction (treatment x photoperiod, F(4, 119.91) = 10.01, fpsyg.2017.00209 p < 0.001), nested interaction (time of day within photoperiod, F(6, 206.20) = 11.17, p < 0.001), and main effects of both treatment (F(4, 74.09) = 3.14, p = 0.019) and photoperiod (F(1, 177.54) = 27.29, p < 0.001). Again, moderate and high dose JZL reduced the number of REM bouts across the LP (t(90.894) -3.41, p 0.002). The number of REM bouts was reduced at multiple time points during the LP following JZL administration (moderate dose, ZT03-06: t(227.24) = 3.19, p < 0.001); high dose, ZT00-09: t(227.24) -2.85, p 0.019). Thus, REM sleep is markedly suppressed by acute augmentation of 2-AG tone, but only when this drug is administered immediately before the time of SART.S23503 day when mice engage in most of their REM sleep. EEG Power Spectral Measurements. Given the effects of increased 2-AG signaling on NREM and REM sleep described above, we examined the spectral content of the EEG signal from the experiment where JZL was administered before the DP (Fig 7). Similar results.
