Restricted feeding restores rhythmicity in the pineal gland of arrhythmic suprachiasmatic-lesioned rats

In mammals, the rhythmic synthesis of melatonin by the pineal gland is tightly controlled by the master clock located in the suprachiasmatic nuclei (SCN). In behaviourally arrhythmic SCN-lesioned rats, we investigated the effects of daily restricted feeding (RF) on pineal melatonin synthesis. RF restored not only a rhythmic transcription of the rate-limiting enzyme for melatonin biosynthesis [arylalkylamine-N-acetyltransferase (AANAT)] and a rhythmic expression of c-FOS but also a rhythmic synthesis of melatonin in the pineal gland. In control rats without functional SCN and fed ad libitum, a daily immobilization stress did not restore any rhythmicity in the pineal gland. Interestingly, a combination of RF and daily stress prior to the time of food access did not markedly impair AaNat mRNA and c-FOS rhythmicity but did abolish the restoration of rhythmic pineal melatonin. These data indicate that the synchronizing effects of RF on the pineal rhythmicity are not due to, and cannot be mimicked by, high levels of circulating glucocorticoids. In keeping with the multi-oscillatory nature of the circadian system, the rhythmicity of pineal melatonin in mammals, until now an exclusive output of the SCN, can also be controlled by daily feeding cues when the SCN clock is lacking. Thus, the present study demonstrates that daily RF in SCN-lesioned rats provides, probably via sympathetic fibres, synchronizing stimuli strong enough to drive rhythmicity in the pineal gland.