| Summary: | 碩士 === 慈濟大學 === 神經科學研究所 === 91 === The principal biological pacemaker in mammalian brains is the hypothalamic suprachiasmatic nucleus (SCN), which controls a number of circadian rhythmic behaviors that includes locomotor activity, hormone secretion, and gene expression. Although the hypothalamic SCN dominantly controls the circadian rhythm, it is also regulated by many environmental and internal cues, such as light pulse and neurotransmitters/neuropeptides. Melatonin is one of the major neuromodulators on the SCN’s rhythmicity both in vivo and in vitro. However, whether all rhythmic behaviors are affected by melatonin through modulation of SCN activity is unclear. The major focus of this study is to determine the roles of endogenous and exogenous melatonin on the regulation of circadian feeding pattern. Adult male Sprague-Dawley rats, weighing between 300 and 500 g, were used in this study. Rats were intraperitoneally injected with melatonin by different doses (1~10 mg/kg) at different time points (1~6 hr). In attempts to block the biological effects of endogenous melatonin, we delivered the neurotoxins, namely 6-hydroxydopamine and 5,7-dihydroxytryptamine, to pineal gland to interfere with the innervations from catecholaminergic neurons and pineal parenchymal cells, respectively. In addition, the pineal gland was surgically removed for eliminating the melatonin synthesis in the brain. Additionally, we also injected the luzindole (24 mg), an antagonist of melatonin MT2 receptors, through the pre-implanted intracerebroventricular cannula. The food consumption of rats was measured every 1, 2, or 4 hr as an index for feeding pattern. In the first section of this study, we found that daily food consumption may serve as an index for circadian rhythm. The phase delay of feeding pattern induced by jet lag restored after 4-5 days. In the second part, we found that the exogenous melatonin treatments failed to change the circadian feeding pattern, either by the different doses or by the different time points in rats. In the third part, the surgical pinealectomy had no effect on the circadian pattern of food intake but influenced the light-on feeding consumption. However, the functional inhibition of pineal gland by neurotoxins failed to result in similar effect of the light-on feeding consumption as caused by pinealectomy. The MT2 antagonist did change the circadian feeding pattern in rats. Finally we found that exogenous melatonin failed to accelerate the phase advance or phase delay of circadian feeding pattern induced by jet lag. In summary, the exogenous melatonin did not affect the circadian feeding pattern, but the removal of endogenous melatonin did change the circadian pattern of food intake. In conclusion, these data showed that melatonin might play the modulatory role on the circadian pattern of food intake in rats.
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