Intracerebral oxytocin modulates sleep-wake behaviour in male rats

Oxytocin released within the brain under basal conditions and in response to stress is differentially involved in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis. Because the HPA axis plays an important role in the regulation of wakefulness, central oxytocin may modulate sleep-wake behaviour. In the present vehicle-controlled study, we assessed the influence of a selective oxytocin receptor antagonist (des-Gly-NH(2)d(CH2)(5) [Tyr(Me)(2), Thr(4)] OVT; 0.75 mug/5 mul) or of synthetic oxytocin (0.1 mug and 1 mug/5 mul), infused into the lateral ventricle (icv), on the sleep pattern in male Wistar rats (n = 7). Compared to vehicle, the oxytocin antagonist slightly but persistently increased wakefulness at the expense of all sleep states. This finding indicates that endogenous brain oxytocin promotes sleep. However, acute icv infusion of oxytocin delayed sleep onset latency, which resulted in a transient reduction of non-REMS and REMS, and augmented high-frequency activity in the electroencephalogram (EEG) within non-REMS. These observations agree with previous reports that icv oxytocin induces a state of arousal. Based on these findings, we postulate that oxytocin has a dual mechanism of action in dependence of the physiological state. Under basal, stress-free conditions, endogenous oxytocin may promote sleep. Conversely, the high brain levels of oxytocin after central oxytocin infusion may reflect a condition of stress accompanied by behavioural arousal and, possibly via an excitatory action on the CRH system, increase vigilance. (C) 2003 Elsevier Science B.V. All rights reserved.