Stylianos Nicolaidis

Dependence of sleep on nutrients' availability

Abstract Continuous EEG recordings were performed in lean (240–250 g) rats, in large size (300–380 g) rats and in Ventromedial Hypothalamic (VMH) lesioned obese (450–470 g) rats, during 4 days of food deprivation and 3 days following food restitution. Though the daily amounts of both Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) were dramatically decreased in lean rats (particularly during the dark phase of the day) by the food deprivation, they remained unchanged in large size rats and also in VMH obese rats. In the latter, there was even a tendency to an increase of SWS during the first two days of starvation. Food restitution brought about a significant rebound in SWS and PS (largely based upon an increase during the dark phase of the diurnal cycle) in lean rats, but had no effect on the sleep parameters of large size and VMH obese rats. Replacement by glucose infusions (100% of the normal daily caloric intake) via a cardiac catheter of oral nutrients in food deprived rats also resulted in a similar increase of sleep duration. These findings suggest that sleep is dependent on the degree of availability of metabolizable substances at the cellular level. In addition, possible causative relations between sleep and feeding are discussed.

Electrical stimulation of the ventromedial hypothalamus enhances both fat utilization and metabolic rate that precede and parallel the inhibition of feeding behavior.

The effects of ventromedial hypothalamic (VMH) stimulation on various metabolic parameters in freely moving animals were measured using a specific indirect calorimetric chamber associated with a quantitative measurement of locomotor activity, which allows the separate measurement of locomotor energy expenditure from that of background metabolism, BM (free from expenses due to locomotion). To obtain circumscribed VMH stimulation, a slight-intensity (20-25 microA) bipolar, constant current was applied for 15 min at the beginning of the dark phase on ad libitum fed rats. The VMH stimulation suppressed feeding for 40 min, then animals progressively recovered within the subsequent 60 min as shown by comparison with the control group. On different days, the same stimulation parameters were applied while food was unavailable, and metabolic parameters were recorded. An increase in BM lasting 30 min was observed. This increase in metabolic rate was sustained by means of a recruitment of lipid stores as indicated by a concomitant drop in respiratory quotient. These observations indicate that the VMH is part of the sympathetic nervous system, capable of inducing lipolysis. The sequence of metabolic and feeding events may then in part be due to VMH-induced lipolysis that provides more fuel to the metabolic economy, raising the BM, which in turn decreases hunger.

Regulatory drinking in rats with permanent access to a bitter fluid source

Male rats were given a quinine adulterated fluid as their sole source of liquid for over 60 days. After a latency of a few days, fluid intake stabilised at about 20 ml/day, with the water to food ratio close to 1.0 ml/g. Bodyweights fell to 90 percent of control levels (rats drinking unadulterated water). A battery of dipsogenic challenges was administered. Compared to controls, the ingestive responses during elevated ambient temperature, hyperosmotic salty food, after fluid deprivation, and to extracellular fluid depletion, were all attentuated. Drinking to acute NaCl injections was totally abolished. The intake of the adulterated fluid was near zero during food deprivation, and when a vegetable and fruit diet was available. Body fluid changes were suggestive of a net dehydration in the quinine drinking rats. Parallels with self intravenous drinking rats and rats recovered from lateral hypothalamic lesions were considered, and possible fundamental differences between natural and nonatural thirst stimuli.

Spontaneous feeding-related monoaminergic changes in the rostromedial hypothalamus revealed by microdialysis

The activity of hypothalamic monoamines in response spontaneous feeding was investigated using the in vivo technique of brain microdialysis together with the instrumental recording of feeding pattern. The simultaneous variations of dopamine (DA), serotonin (5-HT), and their respective metabolites, DOPAC and 5-HIAA, were measured in the rostromedian hypothalamus, where the probe was located between the PVN and VMH. Throughout the experiment, the changes in DOPAC followed a mirror image of those in DA: DA regularly increased, reaching its zenith within the 15-min sample collected during the meal before returning to the same level as just before the meal. Following a premeal plateau, both 5-HT and 5-HIAA increased as soon as the beginning of feeding; 5-HT reached its zenith during the meal while 5-HIAA showed a more delayed and prolonged increase. When a new meal was initiated, 60 to 70 min later, a similar monoaminergic pattern was observed again. These data suggest that building up hunger is announced by an ascending slope of DA and setting up of satiation is concomitant with a descending slope of DA. Concerning serotonergic changes, the sharp 5-HT release during the meal would be a signal of satiation (transient preabsorptive fullness) while the longer-lasting increase in 5-HIAA, reflecting 5-HT synthesis, would be associated with satiety (more persistent postabsorptive state substituting satiation). These data partially confirm and extend previous pharmacological studies as well as the findings on deprivation-induced, imposed meals. They suggest a possible causal relation between monoaminergic changes and behavioral initiatives.

Adaptive changes in energy expenditure during mild and severe feed restriction in the rat

Using a new-generation open-circuit calorimeter capable of monitoring the cost of activity, and thereby both the real thermic effect of feeding (TEF) and basal metabolism in free-moving freely-feeding rats, we have reassessed the proposal that when food intake is restricted an adaptative reduction in energy expenditure participates in the achievement of energy balance. Total energy expenditure, energy expenditure due to spontaneous activity, TEF, basal energy expenditure and respiratory quotient (RQ) were computed by indirect calorimetry in rats given either a mildly restricted (MR) feed intake for 20-30 d (17 g feed/d) or a severely restricted (SR) feed intake for 1-10 d (4 g feed/d). In MR rats no significant changes in any of the measured variables were observed. In contrast, SR rats exhibited an adaptative reduction in energy expenditure due to a reduced spontaneous activity and probably also due to a reduced basal energy expenditure. On the other hand none of the animals fed on a restricted feed intake showed an adaptative TEF decrease, suggesting that TEF under ad lib. feeding is rather an obligatory process that does not include an adaptative component. Taken together, these results point out that under restricted feeding most of the decrease in energy expenditure is associated with simple passive mechanisms, such as body weight loss, and with the reduced feed intake per se. Only under severe feed restriction can some additional energetic economy be obtained from a possible reduction of basal metabolism, and to some extent from reduced activity.

Hypertension induced by electrical stimulation of the subfornical organ (SFO)

In urethane anaesthetized rats, electrical, low intensity stimulations using bipolar concentric electrodes or monopolar glass pipettes were applied to SFO and to surrounding structures populations. Blood pressure, recorded from the femoral artery, was systematically and rapidly increased when the electrical, as well as the mechanical (electrode displacements) stimulations were located within the SFO populations. Remote from the SFO, stimulations either were ineffective or produced non reliable responses. SFO cells seen to be involved in the defense against all hydroionic deficiencies, including those of blood pressure.

A new approach of sleep and feeding behaviors in the laboratory rat

Abstract Sleep and feeding patterns were recorded in 24 rats housed in normal laboratory cages (control) and in niche equipped cages with either a foodcup continuously illuminated or not illuminated (experimental) for 10 to 15 consecutive days. The niche conditions brought about a complete disappearance of nibbling, a significant reduction in the daily number of meals (6.8 vs 9.3) and a significant increase in mean meal size. Though the daily food intake remained unchanged, body weight gain was significantly increased. When the foodcup is illuminated, meals were equally distributed between light and dark phases. Parallel to the latter, sleep durations (particularly Paradoxical Sleep) were increased during the dark phase tending towards an equal circadian distribution. Under the niche conditions, meal size was correlated with the post-prandial events (meal-to-meal intervals and sleep durations within them) during the dark phase as it was during the control period. However, unlike control animals, there were also correlations during the light phase. These results suggest that under the niche conditions, there is a stronger physiological (metabolic) motivation of meal taking and sleep occurrence. Henceforth, such an ecological artifact could be used in order to perform experiments aimed at a better understanding of behavioral regulatory mechanisms.

Feeding and hyperglycemia induced by 1,5-anhydroglucitol in the rat

Abstract 1,5-Anhydroglucitol (1DG, minus an oxygen on carbon 1 of the glucose molecule), has been known physiologically to be present in human cerebrospinal fluid. In order to clarify direct evidence concerning 1DG-induced feeding, hyperglycemia and adrenomedullary mediation of hyperglycemia, 1DG was infused into rat lateral ventricle in doses of 11.8, 21.0, 33.7 and 50.0 μmoles/rat, and its effects compared to those of 2-deoxy-D-glucose (2DG). A dose-dependent increase in food intake after 1DG was 1/3.4 to 1/10.6 of that produced by equimolar 2DG. After 1DG serum glucose concentration gradually increased, peaked at 30 min, and subsequently decreased. Hyperglycemia induced by 1DG was 1/2.1 to 1/2.2 of that produced by 2 DG and was reduced 81% following adrenomedullectomy, which was close to the value for 2DG: 80%. Results were consistent with known differences in the biochemical actions of 1DG and 2DG at the level of substrate specificity of the hexokinase and the rate of glucose transport. These actions suggest that 1DG could provide physiological signals for food intake.

A lateral hypothalamic D1 dopaminergic mechanism in conditioned taste aversion

The aim of this study was to elucidate the role of the neuropil located in the LHA in the acquisition of the association between a taste (conditioned stimulus = saccharin) and a visceral distress (unconditioned stimulus = lithium chloride) leading to long delayed learning of a conditioned taste aversion (CTA). In 82 male rats guide-cannulae were directed bilaterally into the basolateral LHA where bilateral microinjections were made after the conditioned stimulus and before the unconditioned stimulus. We found that: (1) tetrodotoxin, a non-specific blocker of neuronal activity disrupted the acquisition of the CTA; (2) SCH 23390, a specific D1 receptor blocker also disrupted learning of the CTA, while sulpiride, a D2 receptor blocker, did not; (3) neither the specific blockade of D1 nor of D2 receptors could prevent the visceral distress-induced decrease in water intake, showing that the visceral distress was actually experienced; and (4) the sham taste aversion learning (i.e. without visceral distress) revealed that neither the D1 nor the D2 receptors blockade induced by themselves either a taste preference or a taste aversion towards saccharin, indicating that the impaired acquisition of the CTA was not due to a superimposed taste preference that could have been induced by the intra-LHA D1 receptors blockade. It is concluded that the neuropil in the LHA is necessary in the process of the acquisition of long delayed learning and that it uses a D1 receptor specific mechanism.

Spontaneous and 2DG Induced metabolic changes and feeding: The ischymetric hypothesis ☆

A computer-controlled calorimeter which simultaneously measured respiratory exchanges, locomotor activity, and meal patterns, was used to study Total Metabolic Rate (TM), Locomotor Free Metabolic Rate (LFM), and Respiratory Quotient (RQ) in relation to spontaneous and 2DG induced Food Intake in freely-feeding rats. It appeared that spontaneous and 2DG induced feeding was preceded by a consistant drop of LFM starting about five minutes before a meal and reaching its nadir at the onset of a meal. The simultaneous determination of the RQ did not show any systematic change that would have reflected either a lipo- or a gluco-privic origin of the LFM drop and meal onset. Therefore, the results are in agreement with the ischymetric hypothesis of the control of food intake which proposes that the final signal triggering hunger and satiety is the intensity of cell power production (measured in this experiment through the LFM parameter) which is independent of the glucidic lipidic or protidic origin of the substrate(s) supplying power production.