Ghrelin is a 28-amino acid peptide, produced by the stomach and hypothalamic neurons. It is the endogenous ligand of the growth hormone secretagogue receptor 1a. Ghrelin receptors are expressed by various brain regions, such as the arcuate nucleus, lateral hypothalamus, VMH and suprachiasmatic nucleus, Evofosfamide inquirer structures known to be involved in feeding and sleep regulation. Ghrelin secretion is stimulated by fasting and ghrelin enhances feeding and increases adiposity in rats. Growing body of evidence indicates that ghrelin signaling plays a role in the function of arousal mechanisms. Systemic, intracerebroventricular or intrahypothalamic administration of ghrelin suppresses sleep in rats. Ghrelin receptor KO mice show attenuated arousal responses to food deprivation and to the exposure of novel environment. Ghrelin is also implicated in the function of thermoregulatory mechanisms and in the integration of sleep and thermoregulatory responses. Central administration of ghrelin diminishes the activity of brown adipose tissue, a key effector organ in non-shivering thermogenesis, by suppressing the activity of its sympathetic innervation. The product of the preproghrelin gene play a role in coordinating thermoregulatory/metabolic and sleep responses to metabolic challenges. When fasted in the cold, normal mice develop hypothermic bouts and increased sleep during these hypothermic periods. Ghrelin deficient preproghrelin knockout mice are incapable of mounting sleep responses under these conditions and enter precipitous, lethal, hypothermia. FAS inhibitors, such as C75 greatly suppress ghrelin production by the stomach and the hypothalamus. C75 potently suppresses eating and energy expenditure. Since ghrelin stimulates feeding and transgenic mice with elevated circulating ghrelin levels have increased energy expenditure, it seemed possible that the inhibitory effects of C75 on feeding and energy expenditure are mediated by its suppressive action on ghrelin production. To test this hypothesis, we determined the effects of C75 on feeding, metabolism, sleep and motor activity in ghrelin receptor deficient mice. Our major finding is that systemic injection of C75 suppresses motor activity, REMS, and SWA of the EEG in both normal and ghrelin receptor KO mice. These behavioral and sleep effects are accompanied by decreases in VO2, body temperature and RER. We confirm our and others’ previous findings that spontaneous sleep-wake activity, motor activity and food intake on standard laboratory diet are not affected in ghrelin receptor KO mice. Our results also confirm that C75 elicits robust dose-dependent inhibition of 24-h food intake. The effects of C75 on the daily rhythm of feeding have not been reported before. We show that C75 abolished the diurnal rhythm of feeding. Night-time food intake was decreased to the level normally seen during the day, the rest period in mice. The effects of C75 on motor activity have not been quantified previously. In two studies, no “gross Nilotinib changes” in the activity of mice or no “obvious motoric effects” in rats were observed after systemic injection of C75. In the present study, we quantified the effects of C75 on spontaneous motor activity in two separate sets of experiments, by using two different methods. We found that spontaneous motor activity was decreased after ip injection of C75 as measured both by the movement of implanted transponders over a horizontal receiver in Experiment 1 and by the interruption of infrared beams in Experiment 2. The mechanism of the anorectic effects of C75 is not well understood. It is possible that C75 stimulates satiety circuits and/ or suppresses orexigenic mechanisms or inhibits feeding by eliciting visceral illness.