Auditory entrainment of primate drinking rhythms following partial suprachiasmatic nuclei lesions

Normal rats with chronic cardiac catheters were infused with regular insulin at various doses (0.1 to 0.6 IU/hr). The insulin infusion was limited to the 12 light hours and repeated for 4 consecutive days. Daytime insulin infusion increased the 12 hr cumulative food intake in a dose-dependent fashion. This increase was associated with a compensatory decrease in the subsequent nocturnal intake, so that the 24 hr food intake remained unchanged. Results are discussed in relation to mechanisms involved in the normal circadian rhythms of feeding.     

Interaction between circadian and caloric control of feeding behavior in the rat

Feeding at the beginning of the night is probably dependent on the rat's immediate energy requirements while feeding at the end may have an anticipatory function. This latter feeding peak may be mainly controlled by a circadian pacemaker. The aim of this study was to investigate the relative contribution of satiety signals and circadian pacemakers in the control of feeding behavior. Food intake was monitored after infusion of liquid food into the stomach during several parts of the day-night cycle to prevent a possible influence of oral sensations. It is demonstrated that intragastric infusion is more effective in suppressing intake during daytime and the first half of the dark phase than during the second half of the dark phase. Suppressions of food intake are mainly due to delaying the first occurrence of food ingestion, whereas the size of that meal is less affected. During the last period of the night no significant delay could be brought about. These experiments suggest that in the rat a circadian pacemaker dominates feeding motivation during the end of the night thereby strongly interacting with caloric control of feeding behavior.     

Regulation of feeding behavior in the prepubertal female rat.

Responses to challenges of long-term regulation of feeding behavior were compared between adult and weanling female rats. Adulteration of a high fat diet with NaCl caused both adult and weanling rats to reduce their food intake, but neither group refused to eat. Food deprivation for 24 hr was followed by an increase in feeding for both adult and weanling animals during a period when food intake is normally very low. Continued limited food access to 2 hr during the light period was compensated for by an increase in the normal food intake for this period for both adult and young female rats. It was observed that both adult and weanling rats showed a marked preference for the more dilute glucose solution when given a choice. In addition, both groups maintained a constant caloric intake during presentation of the glucose solutions by adjusting their intake of a solid food source. In each challenge of long-term regulation of feeding behavior, the response of weanling animals was as good or superior to that shown by adults. It is concluded that weanling female rats regulate their feeding just as adults to maintain long-term energy balance. It was also observed that bilateral lesions placed in the ventromedial hypothalamus (VMH) at 21 days of age resulted in reduced daily food intake and retarded body weight gain. Furthermore, young rats with VMH lesions failed to respond to 24 hr of food deprivation or limited food access. These data suggest an important role for the VMH in the long-term regulation of feeding in young rats.     

Time-dependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats

In this study the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the daily regulation of feeding, drinking, locomotor activity, and nestbox occupation was investigated. These behaviors were recorded during and after bilateral infusion of NPY into the PVN of rats during the early (E) or late (L) part of the light phase. Administration of NPY caused a significant increase in feeding behavior at E, but not at L. In contrast to the feeding at E, L feeding was associated with increased water intake following NPY infusion. While locomotor activity was similar in sCSF- and NPY-infused rats at all times of the daily cycle, administration of NPY at L, but not at E increased nestbox occupation during the first few hours of the dark phase. This increased nestbox occupation was not associated with altered food intake or drinking behavior, implying that NPY-treated rats made frequent excursions between nestbox and food hopper/water bottle. Thus, feeding-associated drinking and explorative behavior are time-dependently modulated by NPY in the PVN, independent of locomotor activity.     

Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period

The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease in food intake and body weight of marmots. When infused with insulin into their lateral ventricles (Alzet #2002 minipumps), animals had significantly lower food intake as compared to their food intake during the control period. In addition, these animals lost body weight during the period of the insulin infusion. We suggest that during the summer when marmots are not hibernating and are actively feeding, brain insulin levels may play a role in regulating food intake.     

Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval

The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 microgram/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 microgram/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that tolerance does not develop to the action of CCK-8 to suppress meal size, and the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.     

Nocturnal feeding pattern in the prepubertal rat: influence of the ventromedial hypothalamus (VMH)

Daily feeding patterns, food intake and changes in body weight of male and female prepubertal rats were observed across a period from 21 to 50 days of age. Light/dark differences in feeding were found for both males and females throughout the recorded period, with feeding occurring predominantly during the dark period. The light/dark difference in feeding behavior gradually increased as the animals developed. Bilateral lesions placed in the VMH of female rats at 21 days of age disrupted the light/dark differences in feeding behavior primarily by decreasing dark period feeding. These lesions further resulted in a period of hypophagia and retarded body weight gain as well as a delay in pubertal onset. These data indicate that prepubertal rats regulate their feeding behavior so that food intake occurs principally during the dark period and that the integrity of the VMH is necessary for this regulation.     

Modulation of neuronal histamine in control of food intake

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.     

Influence of anterior subdiaphragmatic vagotomy and TPN on rat feeding behavior.

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and of longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.     

Effects of dopamine D1 and dopamine D2 antagonists on the free feeding and drinking patterns of rats.

In male rats with food and water freely available, the specific dopamine D2 antagonist YM-09151-2 had little effect on total food or water intake across a 24-hr period. However, it produced a substantial dose-related decrease in feeding rate during meals and an enhancement of both meal size and duration. The equivalent parameters for water intake were affected to a much lesser extent. A second dopamine D2 antagonist, remoxipride, had similar effects on feeding patterns and, in addition, raised food intake during the 2 hr after drug administration. A third dopamine D2 antagonist, raclopride, produced a short-lived rise in food intake and a slowing of feeding rate with a nonsignificant increase in meal size at intermediate doses. Higher doses increased the latency to feed and drink. The specific D1 antagonist SCH 23390 had small effects on both total food intake and feeding patterns. Water intake was substantially reduced in the first 2-4 hr after drug administration by an increased latency to drink. The results are interpreted, first of all, in terms of two separate effects of dopamine D2 receptors on feeding behavior: the first mediating positive feedback processes important at meal initiation and the second mediating the preabsorptive effects of food on meal termination. D1 receptors, in contrast, are of greater importance in controlling water intake.     

The pineal gland and opiate-induced feeding

Opiate systems in the brain are thought to play a major, though not exclusive, role in the regulation of intake. The rough correspondence of feeding and pineal activity rhythms in the rat offers the possibility that the pineal may also modulate ingestive behavior. In these studies we measured the possibility that pineal manipulations would influence feeding responses to opiate agonists and the antagonist naloxone. Male rats received one of four treatments (or a corresponding control treatment): pinealectomy, removal of the superior cervical ganglia (SCG), transection of the optic nerves or chronic melatonin treatment (1 mg/kg daily). Pinealectomy and melatonin treatment reduced intake during the first half of the dark period, and removal of the SCG reduced intake during the second half of the light period. The most striking effect was seen after optic nerve transection, which reduced nocturnal and increased diurnal intake. Pinealectomy, but no other manipulation, caused a slight decrease in sensitivity to the inhibitory effects of naloxone on intake. None of the treatments affected daytime feeding responses to morphine, ketocyclazocine, or butorphanol. These results suggest that the pineal gland has a minimal role in modulating the opioid regulation of food intake.     

Influence of reversible obesity on eating behavior, blood glucose, and insulin in the rat.

Excessive food intake, resulting in extreme obesity, was induced in rats by electrical stimulation (three 30-min sessions per day for 3 wk) of the lateral hypothalamus (LH). Outside the stimulation sessions no voluntary food intake occurred duringthese weeks. In the subsequent recovery period, accurate records of spontaneous feeding were made. Blood levels of glucose, insulin, and free fatty acids (FFA)were determined during the stimulation period as well as the recovery period. Duringfeeding elicited by electrical stimulation of the LH in the obese phase, there was alarge increase in the glucose level. The insulin level, very high in the intervals between the stimulation sessions, showed no change, a small decline, or a large decrease,respectively, during stimulation in the morning, the afternoon, or the night. If food was withheld during stimulation, there was a large increase in the glucose level and alarge decrease in the insulin level. The first spontaneous meal after the termination of stimulation was extremely postponed, viz, until the glucose and insulin levels returned to normal for the first time. The insulin response to the first spontaneous mealwas exaggerated. Although in the following period (about 10 days) a rapid decrease inbody weight occurred, food intake was only minimal. The insulin level was high and the glucose levelsubnormal during that period. The insulin and glucose levels were normal again only after recovery of normal body weight and food intake. It is tentatively concluded that the regulation of body energy stores (body weight) is achieved through the control of food intake by circulating insulin and glucose levels.     

Sleep, brain energy levels, and food intake

Background

The feeling of hunger and feeding, a wake–state-dependent behavior, is regulated by specific centers within the hypothalamus. While paraventricular nucleus (PVN), arcuate nucleus (ARC), and dorso- and ventromedial hypothalamus (DMH/VMH) regulate feeding, the lateral hypothalamus (LH) is associated both with feeding and wake/REM sleep regulation. In order to examine the effects of sleep and wakefulness on food intake and body weight, we also measured hypothalamic ATP concentrations, which are known to be involved in feeding behavior and sleep–wake regulation.

Methods

In rats, food intake and body weight was measured during a 24-h light–dark cycle and during 6 h of sleep deprivation (SD) performed by gentle handling. Tissue samples from the PVN, ARC/DMH/VMH, and LH were collected after 6 h of SD and from time-matched diurnal controls. ATP was measured by luciferin-luciferase bioluminescence assay.

Results

Across the 24-h light–dark period, rats consumed approximately 28.13±4.48 g of food and gained 5.22±1.65 g with a positive correlation between food intake and body weight. During SD, while food intake increased significantly +147.31±6.13%, they lost weight significantly (–93.29±13.64%) when compared to undisturbed controls. SD resulted in a significant decrease in ATP levels only in LH (–44.60±21.13%) with no change in PVN, ARC/DMH/VMH region when compared with undisturbed controls.

Conclusion

The results indicate a strong overall correlation between ATP concentrations in the LH and individual food intake and suggest a sleep–wake dependent neuronal control of food intake and body weight.     

Circadian feeding rhythm after hypothalamic knife-cut isolating suprachiasmatic nucleus

Bilateral parasagittal knife-cut between the suprachiasmatic nucleus (SCN) and lateral hypothalamic area (LH) or coronal knife-cut between the SCN and ventromedial hypothalamic nucleus (VMH) resulted in a partial loss of the circadian feeding rhythm in rats; after either operation the rats consumed about 30% of their total daily food intake during the light period. However, after the parasagittal and coronal knife-cuts were made in combination, the circadian feeding rhythm was completely lost (50% food intake during the light period). Rats which lost the circadian feeding rhythm partially or completely showed neither obesity nor anorexia. These findings suggest that there are dual informational pathways from the SCN, possibly between the SCN and LH and between the SCN and VMH, through which circadian time signals generated in the SCN are transmitted to the LH and VMH to drive the circadian feeding rhythm.     

Increased drinking of a nonpreferred NaCl solution during food deprivation in the C3H-HeJ mouse

When food was given ad lib, C3H/HeJ mice showed a progressive decrease in NaCl solution intake as the concentration increased from 0.5–2.5% under single tube or double tube conditions. Under the latter condition, 1.5% NaCl intake volumes were approximately 20% of water intake volumes. However, when restricted to $\text{1}\text{3}$ normal food intake, the mice showed significant increase in the intake of 1.5% NaCl and several animals consumed more salt solution than water. Salt intakes declined to predeprivation levels upon return to free feeding. Since feeding of a sodium deficient diet produced no alteration in intake of 1.5% NaCl, the increase during food deprivation was attributed to hypovolemia rather than hyponatremia.     

Food intake after intragastric meals of short-, medium-, or long-chain triglyceride

Food-deprived Sprague-Dawley rats were given equicaloric intragastric infusions of mixed meals consisting largely of short- (SCT), medium- (MCT), or long-chain triglyceride (LCT). When animals were allowed to feed 20 min after infusion, there was an immediate reduction of food intake that was sustained over the 2 hr feeding period. During the first hour of feeding, the SCT, which is digested and absorbed more rapidly than the MCT or the LCT, was more effective per calorie in reducing food intake than these longer-chain triglycerides. However, during the second hour, cumulative intakes after the different triglyceride infusions were not significantly different. Equicaloric infusions of the MCT and the LCT resulted in equivalent reductions of food intake at all times. The satiety effects of these two triglycerides appear to be related to their caloric properties rather than to chain length. Since the LCT reduced food intake before the absorbed fat could have entered the blood to stimulate satiety·signals, this satiety effect may be mediated by a gastroenteric signal. None of the triglyceride infusions resulted in a conditioned taste aversion suggesting that food intake was reduced through normal satiety rather than through discomfort.     

Decreased feeding in rats following hepatic-portal infusion of glucagon

Male rats received a single hepatic-portal injection of glucagon following mild food deprivation. Cumulative food intake measured after 0.5–20 hr was decreased by the hormone. The absence of a concomitant decrease in water intake suggested a specific effect of glucagon on feeding. This specificity was further demonstrated by the use of an hepatic-portal infusion of glucagon as the unconditioned stimulus for the formation of a conditioned taste aversion which failed to produce avoidance of a novel taste. In contrast, pairing the taste with an intraperitoneal injection of lithium chloride did produce a learned taste aversion. Thus, the decreased feeding following infusion of a low concentration of pancreatic glucagon through a chronic hepatic-portal cannula cannot be attributed to visceral malaise. The relatively specific effect of this hormone on short-term feeding probably results from the activation of hepatic glycogenolysis, with the long-term effect on feeding possibly due to gluconeogenesis.     

The differential effects of intravenously administered 8-OH-DPAT on operant food intake in satiated and food-deprived pigs are mediated by central 5-HT(1A) receptors

It has previously been shown that the intravenous administration of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), increases food intake in satiated pigs and decreases food intake in fasted pigs. The present experiments were conducted to investigate the effects of central administration of the 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-N-2-pyridinyl-cyclohexane carbox-amide maleate (WAY 100635), on the stimulant and depressant effects of 8-OH-DPAT on operant food intake in satiated and hungry pigs. In Experiment 1, 8-OH-DPAT (25 microg/kg) produced an increase in operant feeding during the first 30 min following intravenous administration to satiated pigs. The 8-OH-DPAT-induced hyperphagia was completely abolished by pretreatment with WAY 100635 (0.3 mg) administered by intracerebroventricular injection. In Experiment 2, 8-OH-DPAT (25 microg/kg) administered intravenously 15 min prior to the onset of feeding in pigs that had been fasted for 22.5 h produced a decrease in operant food intake, which was most apparent during the first 30 min of the feeding period. The hypophagic effect was completely abolished by pretreatment with WAY 100635 (0.3 mg icv) administered 30 min before the start of the feeding period. In both experiments, WAY 100635 (0.3 mg icv) did not have any significant effects on feeding. The results of the present study extend previous results in the pig and show that both the hyperphagic and the hypophagic effects of 8-OH-DPAT in satiated and fasted pigs, respectively, are mediated by central 5-HT(1A) receptors.     

A moderate swimming exercise regularly performed throughout the life induces age and sex-related modifications in adaptive macronutrients choice

The ability of laboratory rats to adapt food intake to needs is well-known. The present study investigates changes in this adaptive behavior when animals grow old. A cohort of male and female Lou/c/jall rats was regularly submitted to an exercise throughout their life (6 consecutive days of moderate intensity training (3×15 min/day)). Caloric intake and macronutrients selection during exercise and post-exercise periods were compared to the pre-training period. During swimming, a decrease in both caloric intake and fat selection was observed and an increase in protein intake was specifically seen in female groups. However, males were unable to modify the diet composition (macronutrient rate) from 16 months of age, whereas females were able to do it until 24 months of age. The present results suggest a sex-dependant loss of capacity of adjusting feeding behavior to metabolic needs when animals grow old, may be due to a deterioration of the central control of food intake.     

Inhibitory action of insulin on suprachiasmatic nucleus neurons in rat hypothalamic slice preparations

In order to elucidate a role of insulin on neurons in the suprachiasmatic nucleus (SCN) involved in the generation of circadian feeding behavior, we examined the effect of insulin on SCN neuronal activity at in vitro condition. Bath application of insulin (1-100 microU) mainly inhibited the SCN neuronal activity, and this inhibitory effect was still observed in a Ca2+-free Krebs solution. The present result strongly suggests that insulin directly inhibits SCN neurons and may explain an increase in food intake by insulin infusion into the SCN during the light period.