Physiology & Behavior, Vol. 66, No. 2, pp. 329–335, 1999 © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/99/$–see front matter PII S0031-9384(98)00311-4 329 Enhanced Food-Anticipatory Circadian Rhythms in the Genetically Obese Zucker Rat R. E. MISTLBERGER 1 AND E. G. MARCHANT 2 Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby BC, Canada, V5A 1S6 Received 25 August 1998; Accepted 22 October 1998 MISTLBERGER, R. E. AND E. G. MARCHANT. Enhanced food-anticipatory circadian rhythms in genetically obese Zucker rats. PHYSIOL BEHAV 66(2) 329–335, 1999.—This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food-anticipatory rhythms to daily feeding schedules. Leptin is secreted by adipocytes in proportion to fat content, exhibits a daily rhythm in plasma that is synchronized to feeding time, and inhibits activity of arcu- ate neuropeptide Y neurons that stimulate feeding behavior and regulate metabolism. Activity within this neuropeptide Y system is enhanced by food deprivation and attenuated by overfeeding and diet-induced obesity. Diet-induced obesity, in turn, attenuates food-anticipatory rhythms. If the effects of obesity on food-entrained rhythms are mediated by leptin inhibi- tion of neuropeptide Y neurons, then these rhythms may be enhanced in leptin-insensitive Zucker obese rats. Alternatively, if daily rhythms of leptin mediate the generation or entrainment of these rhythms, Zucker rats may fail to anticipate daily feedings. Zucker obese and lean rats received food for 3 h/day during the midlight period. Both groups exhibited significant food-anticipatory activity that persisted during three cycles of food deprivation, but this rhythm was significantly more robust in obese rats, when expressed as anticipation and persistence ratios, and as peak values. Anticipatory rhythms did not persist in either group when food was provided ad lib. These results indicate that central actions of leptin may mediate the inhibitory effects of obesity on the expression of food-anticipatory rhythms in rats, but do not mediate the inhibitory effects of ad lib food access, and do not serve as necessary internal entrainment cues or clock components for the food-entrainable circadian system. © 1999 Elsevier Science Inc. Circadian rhythms Food entrainment Food restriction Zucker rats Obesity CIRCADIAN rhythms in mammals are regulated by a mul- tioscillator system. The hypothalamic suprachiasmatic nuclei (SCN) are the site of one collection of cell autonomous circa- dian oscillators that function together as the master pace- maker for entrainment of circadian rhythms to light–dark (LD) cycles (27,60). This pacemaker can also be entrained by a variety of nonphotic stimuli that induce locomotor activity or arousal [e.g., (23,30,45,59)]. However, it does not appear to be necessary for entrainment of behavioral, autonomic, and endocrine rhythms to a scheduled daily meal. Food-entrained activity rhythms are characteristically expressed as consoli- dated bouts of running or foraging-related activities that be- gin 1–3 h prior to scheduled feeding, and that increase in in- tensity until feeding time [reviewed in (35)]. This anticipatory activity to a daily feeding event exhibits the circadian proper- ties of persistence during constant conditions (i.e., when food is withheld for several days, activity reoccurs at its usual phase) and circadian limits to entrainment (i.e., anticipation develops only to feeding schedules with intermeal intervals within the circadian range of 22–31 h), indicating regulation by a self-sustaining circadian pacemaker (7,46,54). However, food-anticipatory rhythms in behavior or physiology are nei- ther disrupted nor prevented by complete ablation of the SCN in rats (6,55), hamsters (1,34), and mice (30). At present, neural components of the food-entrainable pacemaker system are unknown (35). One region that has not been directly evaluated for a role in food entrainment is the arcuate nucleus (ARC)–neuropeptide Y (NPY) system that has been implicated in the regulation of feeding behavior and energy homeostasis. Several observations indicate that activ- ity within this system correlates with and may drive or modu- late circadian food anticipatory activity. The ARC includes NPY-containing neurons that innervate several hypothalamic nuclei, including the paraventricular and dorsomedial hypo- 1 To whom requests for reprints should be addressed. E-mail: mistlber@sfu.ca 2 Current address: Department of Psychiatry, SUNY at Stony Brook, NY, 11794.