Institute of Neuroscience

Second only to light, daily restricted feeding schedules can entrain circadian rhythms in mammals Terman, 1980, Stephan, 2002). Contrary to light, however, such feeding schedules have been found not to affect the master circadian clock in the suprachiasmatic nucleus (SCN) .

Abbreviations: CEA, central nucleus of the amygdala; BLA, basolateral amygdala; DG, dentate gyrus; SCN, suprachiasmatic nucleus; PER2, Period2; BNST-OV, oval nucleus of the bed nucleus of the stria terminalis; LD, light dark; LL, constant light, RF, restricted feeding; ZT, zeitgeber time; AL, ad libitum 3 Abstract Restricted feeding schedules (RF) in which daily access to food is limited to a few hours each day can entrain the rhythms of expression of circadian clock genes in the brain and periphery in rodents. The critical factors mediating the effect of RF on rhythms of clock gene expression are unknown. Previously, we demonstrated that daytime RF shifts the phase of expression of the clock protein, Period2 (PER2) in the oval nucleus of the bed nucleus of the stria terminalis in rats kept on a 12-hour light dark cycle, and restored the rhythm of PER2 expression in rats housed in constant light. We now report that RF also modifies the rhythms of PER2 expression in the central and basolateral nuclei of the amygdala and in the dentate gyrus, such that all three areas become synchronized, peaking 12 hours after the time of food presentation. Daily limited access to sucrose or saccharine in freely fed rats or scheduled access to saline in sodium-deprived rats had no effect on these PER2 rhythms. Thus, it would appear that the rhythms of PER2 in limbic forebrain structures are sensitive to signals that arise from the alleviation of a negative metabolic state associated with scheduled feeding and that access to rewarding substances in the absence of food deprivation or metabolic challenges, per se, are not sufficient to alter the rhythms of PER2 expression in these regions.

Ghrelin, an orexigenic hormone produced by the stomach, is secreted in anticipation of scheduled meals and in correlation with anticipatory locomotor activity. We hypothesized that ghrelin is directly implicated in stimulating locomotor activity in anticipation of scheduled meals. To test this hypothesis, we observed 24 h patterns of locomotor activity in mice with targeted mutations of the ghrelin receptor gene (GHSR KO) and wild-type littermates, all given access to food for 4 h daily for 14 days. While wild type (WT) and GHSR KO mice produced increases in anticipatory locomotor activity, anticipatory locomotor activity in GHSR KO mice was attenuated (P<0.05). These behavioral measures correlated with attenuated levels of Fos immunoreactivity in a number of hypothalamic nuclei from GHSR KO placed on the same restricted feeding schedule for 7 days and sacrificed at ZT4. Interestingly, seven daily i.p. ghrelin injections mimicked hypothalamic Fos expression patterns to those seen in mice under restricted feeding schedules. These data suggest that ghrelin acts in the hypothalamus to augment locomotor activity in anticipation of scheduled meals.

Ghrelin, the 28 amino acid peptide recently identified as the natural ligand for the growth hormone (GH) secretagogue (GHS) receptor, has multiple activities in addition to stimulation of GH secretion, including stimulation of feeding and weight gain. To utilize these actions for ...

By definition, parental care behaviors increase offspring survival, and individual fitness, at some cost to the parent. In smallmouth bass (Micropterus dolomieu), parental males provide sole care for the developing brood that includes an increase in activity during brood defense and decreased foraging resulting in a decline in endogenous energy reserves. No mechanisms have been proposed for cessation of voluntary foraging, though regulation of appetite hormones such as ghrelin have been documented to affect feeding behavior in other fishes. We documented baseline fluctuations in plasma ghrelin concentrations across parental care. Plasma ghrelin concentrations were lowest during the early stages of parental care before increasing as the brood developed to independence. Additionally, we performed an intervention experiment whereby plasma ghrelin levels were artificially increased through an injection of rodent ghrelin at the onset of parental care. Despite measuring a significant increase in plasma ghrelin approximately 1 week after injection, we noted no differences in plasma-borne indicators of recent foraging activity indicating that voluntary anorexia is possibly reinforced by receptor insensitivity to appetite hormones. Finally, we assessed the ultimate consequences of foraging during parental care by feeding fish to satiation and measuring post-prandial changes in swimming performance and aggression. Fish fed to satiation showed significant decreases in burst swimming ability and aggressiveness towards potential brood predators. Voluntary anorexia during smallmouth bass parental care is an adaptive behavior that avoids potentially deleterious declines in swimming performance and aggression apparently through a modulation of production and reception of appetite hormones including ghrelin.

Leptin administration has been shown to prevent the disruptive effects of acute food deprivation on reproductive function in cycling females and lactating females. We examined the ability of intracerebroventricular leptin administration to ameliorate the effects of food restriction for the first 2 wk postpartum on length of lactational infertility. Leptin administration did not reduce the effects of food restriction on reproductive function at either time period ( days 8-15 and 15-22 postpartum) or dose (1 and 10 μg/day) administered. Because of the sharp contrast between these results and the ability of leptin to offset the effects of acute food deprivation in lactating rats, the remaining studies investigated the possible causes of this difference. Both central and peripheral leptin administration eliminated food deprivation-induced prolongation of lactational infertility, suggesting that neither route of administration nor dose was a factor. However, we noticed that, whereas chro...

Uncoupling protein 2 (UCP2) is known to promote neuroprotection in many forms of neurological pathologies including Parkinson's disease. Here, we examined the hypothesis that UCP2 also mediates aspects of normal nigrostriatal dopamine (DA) function. Mice lacking UCP2 exhibited reduced dopamine turnover in the striatum as measured by the 3,4-dihydoxyphenylacetic acid ⁄ dopamine (DOPAC ⁄ DA) ratio, reduced tyrosine hydroxylase immunoreactivity (TH IR) in the substantia nigra pars compacta (SNc) and reticulata, striatum and nucleus accumbens. UCP2-knockout (KO) mice also had reduced dopamine transporter immunoreactivity (DAT IR) in the SNc but not other brain regions examined. In order to determine if these biochemical deficits are transcribed into behavioural deficits, we examined locomotor function in UCP2-KO mice compared to wild-type (WT) controls. UCP2-KO mice exhibited significantly reduced total movement distance, movement velocity and increased rest time compared to wild-type controls. These results suggest that UCP2 is an important mitochondrial protein that helps to maintain normal nigrostriatal dopamine neuronal function and a reduction in UCP2 levels may predispose individuals to environmental causes of Parkinson's disease.

Plevious rtudies have dernonhtratcd that food restricken during Ii&%&on extends the length of lact,kmal inlcrtiliQ III Iilk In order lo determine whether Neuropcptide Y (NPY) plays a role in the increased length of lactational infertility xen in food-reslricted rals, NPY immunortxctivity in the arcuale nucleus of lactating rats that were ad lib fed or food restricted from Day 8 to I3 postpartum was compared. Food-restricted rats showed higher numbers of NPY-stained cells ut the end of the food-restriction period (Day I.5 poslparium) than did ad lib-fed rats at the Same stage of lactation. This difference persisted until Day 25 postpat?um although all animals were fed ad libitum from Day 15 onwards. Switching litters between ad lib-fed and food-restricted females from Day 15 until Day 20 postpartum did not eliminate the difference in NPY immunorextivity bctwcen the two diet conditions. Given !har food restriction during lactation lemls to u prolonged suppression of LH release that nlso persists crftcr refeeding and is not aff;ctcd by the nutritionnl statuh of the litter. thc~ dutu arc consistent with il role for NPY in the prolonged suppression of rcprodtlciavc function uxn in toad rewlctrd lactating rat*.

A review is provided of current evidence supporting the actions of the stomach-derived peptide ghrelin on ventral tegmental area (VTA) dopamine cells to increase food intake and other appetitive behaviours. Ghrelin is a 28 amino-acid peptide that was first identified as an endogenous ligand to growth hormone secretagogue receptors (GHS-R). In addition to the hypothalamus and brain stem, GHS-R message and protein are distributed throughout the brain, with high expression being detected in regions associated with goal directed behaviour. Of these, the VTA shows relatively high levels of mRNA transcript and protein. Interestingly, ghrelin infusions into the VTA increase food intake dramatically, and stimulate dopamine release from the VTA. Moreover, VTA dopamine neurones increase their activity in response to ghrelin in slice preparations, suggesting that ghrelin increases food intake by modulating the activity of dopaminergic neurones in the VTA. On the basis of these data as well as the fact that VTA dopamine cells respond to other metabolic hormones such as insulin and leptin, it is proposed that VTA dopamine cells, similar to cells in the mediobasal hypothalamus, are first-order sensory neurones that regulate appetitive behaviour in response to metabolic and nutritional signals.

Psychopathologies, such as depression, are frequently accompanied by poor coping strategies, including impaired social support resources. As well, unsupportive social interactions have been related to adverse health outcomes beyond any contribution of limited social support resources. There is reason to believe that increased eating associated with stressors represents a method of coping, albeit one that has negative consequences. The present investigation examined the relation between both unsupportive and supportive social interactions and emotional eating, and assessed whether this relationship was mediated by individual coping styles. Study 1 (N = 221) indicated that unsupportive social interactions were associated with emotional eating, and with emotion-and avoidant-focused coping. Furthermore, multiple mediation analyses indicated that emotion-focused coping mediated the relation between unsupportive social interactions and emotional eating. Study 2 (N = 169) replicated these findings, and also indicated that these effects were above and beyond those of social support and depressive symptomatology. Thus unsupportive social interactions may have implications for health outcomes and behaviors, beyond mood disorder symptomatology. The observed relations can be explained by theories of affect-regulation such as negative urgency and expectancy theory as well as on the basis of biological processes associated with eating and stress responses.