Circadian variations in the inhibition of dopamine release from adult and newborn rat hypothalamus by melatonin

The inhibitory effect of melatonin on evoked dopamine release from the hypothalamus was studied in adult male rats throughout a 24-hour period. The animals were maintained under a daily schedule of 14 h of light (0.00-14.00 h) and 10 h of darkness. The inhibition of dopamine release in vitro by 1 μM melatonin clearly exhibited a 24-hour rhythm with a peak at 5.00 h and almost no inhibition at 15.00 h. The concentrations of melatonin needed to produce this effect were similar throughout the 24-hour cycle, although the actual amount of inhibition at any given concentration of melatonin varied. Other indole derivatives, with the exception of 5-methoxy tryptophol, did not affect significantly the release of 'H-dopamine from the male rat hypothalami. The inhibition of dopamine release by melatonin was not observed in newborn rats but developed during the first week of life, reaching a plateau level between 6 and 7 days postnatally. However, the difference between the amount of inhibition by melatonin at 5.00 h and at 8.00 h existed from the time the inhibition was first observed. The change in amplitude of this difference was due not to differences in the apparent affinity towards melatonin but to increase in the maximal inhibition observed at 5.00 h. The data indicate that the hypothalamic sensitivity to melatonin exhibits a circadian rhythm, and that this develops postnatally prior to the development of circadian variations in melatonin levels, i.e. the 'melatonin rhythm'. In addition, the data suggest that the occurrence of the diurnal rhythm in sensitivity is not simply the consequence of a down-regulation of melatonin receptors by melatonin released from the pineal gland the previous night.