Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle.

STUDY OBJECTIVES: Though melatonin and melatonin receptor agonists are in clinical use and under development for treating insomnia, the role of endogenous melatonin in the regulation of the sleep-wake cycle remains uncertain. Some clinical case reports suggest that reduced nocturnal melatonin secretion is linked to sleep disruption, but pineal-gland removal in experimental animals has given variable results. DESIGN: The present study examined the effects of pinealectomy on the diurnal sleep-wake cycle of rats implanted with a radiotransmitter to allow continuous measurement of cortical electroencephalogram, electromyogram, and core temperature (Tc) without restraint in their home cages. MEASUREMENTS AND RESULTS: Tc was slightly (0.2 degrees C) but significantly lower after pineal removal. The total amount and diurnal distribution of locomotor activity, wake, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were unaltered in pinealectomized rats compared to sham-operated controls. Sleep consolidation measured by determining wake, NREM sleep, and REM sleep bout length and frequency was also unchanged. The EEG power spectrum during NREM sleep was unchanged, but a significant decrease in theta power (5-8 Hz) during REM sleep episodes was found. CONCLUSIONS: Our data provide no evidence that endogenous circulating melatonin plays a role in regulating the sleep-wake cycle in rats. However, because cortical theta oscillations are generated in the CA1-3 layer of the hippocampus, neurons known to express melatonin receptors, this suggests that a lack of melatonin following pineal removal influences the function of these neurons and is consistent with previous work suggesting that endogenous melatonin is an important regulator of hippocampal physiology.