Hypnotic Effects of Melatonergic Compounds Measured in Mice or Rats

Melatonin is a pleiotropic compound mostly acting through its two G protein-coupled receptors named MT1 and MT2 and known for its role in regulating the sleep/wake cycle and circadian rhythms. Although this is common belief, there has been long debate in the scientific community on whether melatonin or melatonergic compounds are endowed with hypnotic effects. One of the reasons for this debate relied on contrasting findings in the literature in part due to non-standardized methods across studies in examining at preclinical level the effect of melatonin or melatonergic compounds on the sleep/wake cycle. Here, we describe a method in mice and rats to evaluate the effect of melatonin or melatonergic compounds on the different stages of the sleep/wake cycle, providing details concerning the administration of the drug and the analytical procedure for scoring the electroencephalogram/electromyogram (EEG/EMG) recording.