The effects of an intravenous application of melatonin upon eye movements and muscular tonus were examined in acute decerebrate cats in order to elucidate whether melatonin can be beneficial as a therapeutic agent for treating sleep disturbance. The results were compared to those produced by an intravenous application of diazepam, one of the benzodiazepines, and from a microinjection of carbachol, a cholinergic agent resistant to cholinesterase, into the pontine reticular formation. The application of melatonin produced neither changes in muscle tone nor in eye movements in cats in which the decerebration was made at the level of precollicular-postmammillary level (mesencephalic cats). However, it did produce rapid eye movements (REM) with muscular atonia in the cats in which the decerebration was performed at the level of precollicular-precollicular-preoptic chiasma level (hypothalamic cats). In the latter preparation, the suprachiasmatic nucleus (SCN) was preserved. Although an application of diazepam abolished muscle tone, it did not change eye movements in either mesencephalic or hypothalamic cats. An intrapontine carbachol injection resulted in muscular atonia associated with REM in the mesencephalic cats. These results suggest that the melatonin application activates SCN neurons, which, in turn, trigger REM sleep generating system in the brainstem. However, muscle tone suppression induced by the diazepam application may not be a result of the activation of the brainstem REM sleep generating system. We propose that melatonin would be a more useful and safe therapeutic agent for treating sleep disturbances than conventional drugs such as benzodiazepines.
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