Melatonin microinjection into the medial preoptic area increases sleep in the rat

A wide variety of hypnotic compounds including triazolam, pentobarbital, ethanol and adenosine have been reported to enhance sleep when microinjected into the medial preoptic area (MPA) of the anterior hypothalamus of the rat. It is uncertain whether the pineal hormone melatonin, which may alter sleep/wake physiology in mammals, acts at this site. A previous report has indicated that a more widespread injection of melatonin into the hypothalamus of the cat induces sleep. In the present study we have examined the possibility that the MPA may mediate this effect. Nine adult rats were microinjected with melatonin 1 and 50 ug and vehicle into the MPA during the daytime in a repeated measures design study. It was found that melatonin increased total sleep time in a dose-dependent manner, primarily by increasing NREM sleep, and that wake time after sleep onset was significantly reduced. These data add melatonin to the growing list of compounds that increase total sleep after administration into the MPA, and suggest that the MPA may be a common site of action for such agents from a variety of pharmacologic classes. Based on previous studies, the possibility is raised that this sleep enhancement results from an alteration in function of the GABA(A)-benzodiazepine receptor complex.