Quiet wakefulness: The influence of intraperitoneal and intranasal oxytocin on sleep-wake behaviour and neurophysiology in rats

Abstract

Introduction: Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioural processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest and promote sleep. At present, little research has comprehensively characterised the neuropsychopharmacology of oxytocin-induced effects on sleep-wake behaviour and no reconciliation of these two competing hypotheses has been proposed. Methods: This study explored the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg-1) and intranasal (i.n.; 0.06, 1, 3 mg·kg-1) routes. Caffeine (i.p. and i.n.; 10 mg·kg-1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pre-treatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg-1) followed by oxytocin (i.p.; 1 mg·kg-1) were also conducted. Results: In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, NREM and REM sleep. Several i.p. oxytocin-induced sleep-wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep-wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects. Conclusions: These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep-wake behaviour: i.p. oxytocin promotes quiet wakefulness, a state of restful environmental awareness compatible with both oxytocin-induced anxiolytic effects and its enhancement of processing complex stimuli.