Proton pump inhibition increases rapid eye movement sleep in the rat

Abstract

Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor "lansoprazole" on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg) were injected intraperitoneally in the same animal (n = 7) and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26 ± 1.03 and 9.09 ± 0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle) and 34.21% (from low dose). Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker "amiloride" (10 mg/kg; i.p.) (n = 5) did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.

Figure 1

Percent wakefulness, NREM and REM sleep amount in baseline, vehicle, lansoprazole (low dose), and lansoprazole (high dose) out of total recording time (TRT). Lansoprazole (both low and high dose) did not increase (a) wakefulness and (b) NREM sleep, significantly. However, (c) REM sleep amount significantly increased after high dose (10 mg/kg) of lansoprazole injection (P < 0.01; F _(3,27) = 6.53) (one-way RM-ANOVA with Tukey post hoc tests) compared to vehicle (Tukey, P < 0.01) and low dose (1 mg/kg) lansoprazole (Tukey, P < 0.01) injections (i.p.). ** indicates P < 0.01.

Figure 2

Percent REM sleep amount in baseline, vehicle, lansoprazole (low dose), and lansoprazole (high dose) groups during initial and later three hours of total recording time (TRT). (a) REM sleep amount did not change during the initial three-hour period after injection (P = 0.24; F _(3,27) = 1.52) (one-way RM-ANOVA with Tukey post hoc tests), (b) it significantly increased, however, after three hours of lansoprazole injection (P < 0.05; F _(3,27) = 4.07) (one-way RM-ANOVA with Tukey post hoc tests) compared to vehicle (Tukey, P < 0.05) and low dose (Tukey, P < 0.05). * indicates P < 0.05.

Figure 3

REM sleep episode number, episode length and latency in vehicle, and lansoprazole low and high dose treated animals. (a) REM sleep episode number significantly increased in lansoprazole high dose (10 mg/kg) compared to vehicle and lansoprazole low dose (1 mg/kg) treated rats (P < 0.05; F _(2,20) = 4.82). REM sleep episode duration length (b) and latency (c), however, did not change. * indicates P < 0.05.