Sleep deprivation in the rat: XVI. Effects in a light-dark cycle.

To avoid a possible confound between the effects of sleep loss and disturbed circadian rhythms in previous studies of total sleep deprivation (TSD) by the disk-over-water method, TSD rats and their yoked control (TSC) rats had been maintained in constant light both before and during the experiment. With circadian rhythms of both groups flattened by constant light, group differences in outcome measures could be attributed to sleep loss. However, the constant light control entailed the possibility that the sleep loss effects might obtain only in constant light. To evaluate this possibility, three TSD-TSC rat pairs maintained on a 12 hour light: 12 hour dark (LD) schedule were studied. TSC rats showed only minor changes during the deprivation period. As in previous studies, TSD rats showed increased food intake; decreased weight; increased energy expenditure; debilitated appearance; lesions on the tail and paws; an initial increase followed by a large decrease in body temperature; impending death; and recovery sleep, which featured large, selective, sustained rebounds of paradoxical sleep and a reversal of all observed TSD-induced changes. Thus, TSD produced the same changes during an LD schedule as during constant light. The amplitude of the diurnal body temperature rhythm declined over the course of TSD and then almost completely recovered during the first day of recovery sleep. The decline was interpreted as the result of deprivation-induced thermoregulatory changes.     

Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat

The effects of 24 hr of sleep deprivation on cortical EEG and ventral hippocampus EEG recordings, ventral hippocampus spike rates, sleep stages percentages, and bout length measures were studied in rats. Two groups, differing only in the rate and distance they were forced to walk during deprivation by the water wheel method, were recorded continuously (23 hr per day) for one baseline, one deprivation, and two recovery days. During deprivation, microsleeps, increased hippocampal spike rates, and increased amplitude of the EEG recordings all suggested the intrusion of sleep processes. Nonetheless, there was no evidence to support the idea that these animals were not substantially deprived of sleep. No important differences were found in the recovery data of the two groups, even though one group walked three times as far as the other during deprivation. This supports the idea that, in conjunction with large amounts of sleep deprivation, changes in exercise and energy depletion may have little effect on sleep measures. During recovery, increased hippocampal spike rates and bout lengths, as well as increases in EEG amplitude, were interpreted in terms of increased sleep "intensity." High amplitude NREM sleep rebounded first, followed by rebounds in both paradoxical sleep and low amplitude NREM sleep. This pattern was compared to patterns previously reported for humans, cats, and rats. Finally, the tendency for some measures to fall below their baseline levels after an initial rebound was discussed in terms of "sleep inhibition" and servomechanism theory.     

Electrophysiological evaluation of three paradoxical sleep deprivation techniques in rats

Three different techniques were used to study the effects of 72 hr deprivation of paradoxical sleep on percentages total sleep, light slow wave sleep, deep slow wave sleep and paradoxical sleep during deprivation and recovery periods in rats. The paradoxical sleep deprivation methods used were the classical platform, the pendulum and the multiple platform techniques. The different groups were continuously recorded over a base-line day, three deprivation days and four recovery days. All three groups showed clear suppression of paradoxical sleep throughout the deprivation period, although small differences between the pendulum and the multiple platform technique emerged. The distribution of sleep across the day and the amount of deep slow wave sleep were affected differently. Besides an exception immediately after deprivation, no important differences were detected on the recovery days. The recovery is characterized by an immediate rebound of paradoxical sleep, completed within two days, as well as rapid re-normalization of sleep percentages. A small rebound of deep slow wave sleep was recorded at the end of the dark period during the first three recovery days. Various sleep and non-sleep related variables of the PS deprivation techniques are discussed. It is improbable that the platform-pendulum controversy is due to differences in the amount of PS deprivation or the other sleep parameters measured here. Rather it looks as though non-specific platform effects override the effects of PS deprivation.     

Changes in the sleep-wake cycle architecture and cortical nitric oxide release during ageing in the rat

Changes in sleep-wake states and nitric oxide release were examined in aged rats versus young-adult ones. Sleep-wake recordings and nitric oxide measurements were taken from animals chronically equipped with polygraphic and voltametric electrodes. Animals were examined in baseline conditions and in response to a 24-hour paradoxical sleep deprivation. In aged rats, basal amount of paradoxical sleep is decreased during the light phase versus young-adult animals. After paradoxical sleep deprivation, a paradoxical sleep rebound occurs with an amount and intensity that are less marked in aged animals than in young-adult rats. The amplitude of the circadian distribution for wakefulness, slow-wave sleep and paradoxical sleep amounts is reduced with age. Finally, delta-slow-wave sleep and theta-paradoxical sleep power spectra are attenuated either in baseline conditions or after paradoxical sleep deprivation in aged animals. It is also reported that cortical nitric oxide release exhibits a circadian rhythm with higher amplitude in aged rats than in young-adult ones. However, after paradoxical sleep deprivation, a limited overproduction of nitric oxide is obtained compared with young-adult ones. These results, evidencing the dynamics of the nitric oxide changes occurring in relation to the sleep-wake cycle, point out the homeostatic paradoxical sleep regulation as an age-dependent process in which the nitric oxide molecule is possibly involved.     

Glucocorticoids are not responsible for paradoxical sleep deprivation-induced memory impairments

STUDY OBJECTIVES: To evaluate whether paradoxical sleep deprivation-induced memory impairments are due to release of glucocorticoids, by means of corticosterone inhibition with metyrapone. DESIGN: The design was a 2 (Groups [control, paradoxical sleep-deprived]) x 2 (Treatments [vehicle, metyrapone]) study, performed in 2 experiments: Acute treatment (single injection given immediately after 96 hours of sleep deprivation) and chronic treatment (8 injections, twice per day, throughout the sleep-deprivation period). Animals were either paradoxical sleep-deprived or remained in their home cages for 96 hours before training in contextual fear conditioning and received intraperitoneal injections of a corticosterone synthesis inhibitor, metyrapone. Memory performance was tested 24 hours after training. SUBJECTS: Three-month old Wistar male rats. Measurements: Freezing behavior was considered as the conditioning index, and adrenocorticotropic hormone and corticosterone plasma levels were determined from trunk blood of animals sacrificed in different time points. Animals were weighed before and after the paradoxical sleep-deprivation period. RESULTS: Acute metyrapone treatment impaired memory in control animals and did not prevent paradoxical sleep deprivation-induced memory impairment. Likewise, in the chronic treatment, paradoxical sleep-deprived animals did not differ from control rats in their corticosterone or adrenocorticotropic hormone response to training, but still did not learn as well, and did not show any stress responses to the testing. Chronic metyrapone was, however, effective in preventing the weight loss typically observed in paradoxical sleep-deprived animals. CONCLUSIONS: Our results suggest that glucocorticoids do not mediate memory impairments but might be responsible for the weight loss induced by paradoxical sleep deprivation.     

Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation

OBJECTIVES:

The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats.

METHOD:

Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups.

RESULTS:

Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the food-restricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in food-restricted animals were each decreased compared to both ad libitum groups.

CONCLUSION:

These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk.     

Overcompensation of food intake following brief periods of food restriction

Four adult female Sprague-Dawley rats, maintained on an ad lib feeding schedule were deprived for either 0, 0.5, 1, 2, 4, 6, or 8 hours during the dark phase of the day-night cycle. It was found that the latency to initiate the first meal following the deprivation was independent of the previous deprivation interval. The animals were found to overcompensate for the periods without food by eating a large initial meal that increased proportionately in size with the duration of food restriction. Furthermore, the animals continued to overeat throughout the day. This deprivation-induced overeating by the animals resulted in an overcompensation in total food consumption that was 21–56% greater than on control days. The role of food intake as a regulator of body weight is discussed.     

Period-amplitude analysis of rat electroencephalogram: effects of sleep deprivation and exercise

Electroencephalogram (EEG) wavelength and amplitude within NREM sleep, paradoxical sleep (PS), and wake were measured by computer in five intact rats and four rats with suprachiasmatic nucleus (SCN) lesions for the first recovery day following 24-h total sleep deprivation (TSD) achieved by keeping them on a rotating cylinder over water. To assess exercise effects, EEG within NREM was also analyzed in four intact rats for 8 h after separate 4-h TSD sessions at low and high rates of cylinder rotation (high rate = 12 times low rate). During recovery from 24-h TSD, EEG changed most dramatically in NREM. The number of slow waves per unit time (1-4 Hz wave incidence) and the amplitude at all wavelengths from 1 to 16 Hz were increased for up to 12 h and then fell below baseline levels for most of the next 12 h. Fast (5-16 Hz) wave incidence changed inversely with slow wave incidence. Wake and PS also showed initially increased amplitude, but shifts in incidence were from slow to fast waves. Relative to baseline, intact and SCN-lesioned rats showed similarly shaped recovery functions, indicating that EEG responses to sleep loss are largely independent of diurnal rhythms. Four-hour TSD at a low rotation rate affected NREM EEG similarly to 24-h TSD, but more mildly. The high rotation rate further increased slow wave incidence during recovery without further increasing slow wave amplitude. The results suggest that both EEG wave incidence and amplitude are responsive to prior wakefulness, but only incidence is responsive to prior exercise.     

Paradoxical (REM) sleep deprivation in mice using the small‐platforms‐over‐water method: polysomnographic analyses and melanin‐concentrating hormone and hypocretin/orexin neuronal activation before,during and after deprivation

Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small‐platforms‐over‐water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep. To fulfil this need, we refined this deprivation method and analysed vigilance states thoroughly during the entire protocol. We also studied activation of hypocretin/orexin and melanin‐concentrating hormone neurones using Fos immunohistochemistry to verify whether mechanisms regulating paradoxical sleep in mice are similar to those in rats. We showed that 48 h of deprivation was highly efficient, with a residual amount of paradoxical sleep of only 2.2%. Slow wave sleep and wake quantities were similar to baseline, except during the first 4 h of deprivation, where slow wave sleep was strongly reduced. After deprivation, we observed a 124% increase in paradoxical sleep quantities during the first hour of rebound. In addition, 34% of hypocretin/orexin neurones were activated during deprivation, whereas melanin‐concentrated hormone neurones were activated only during paradoxical sleep rebound. Corticosterone level showed a twofold increase after deprivation and returned to baseline level after 4 h of recovery. In summary, a fairly selective deprivation and a significant rebound of paradoxical sleep can be obtained in mice using the small‐platforms‐over‐water method. As in rats, rebound is accompanied by a selective activation of melanin‐concentrating hormone neurones.     

Influence of stress duration on the sleep rebound induced by immobilization in the rat: a possible role for corticosterone.

In rats, recovery from short intense stress usually involves a sleep rebound characterized by an increase in slow-wave sleep and paradoxical sleep duration. However, a large body of evidence indicates that stressful situations lasting for several days or weeks can have deleterious effects on sleep quantity and quality, probably leading to an impairment of the sleep rebound. In this study, using immobilization as a stress model in the rat, we sought to determine the stress duration beyond which the sleep rebound disappears, as well as the mechanisms responsible for this suppression. In a first series of experiments, rats were immobilized for 30 min, 1h, 2h or 4 h. Slow-wave sleep rebounds evidenced after the different immobilization periods were, respectively, +32%, +25%, +9% and -0.2% and paradoxical sleep rebounds +57%, +88%, +103% and +21% compared with control recordings of the same animals. The sleep rebound thus disappeared when the duration of immobilization reached 4 h. In a second series of experiments, adrenalectomized rats were subjected to a 1 h immobilization, and showed an increased slow-wave sleep rebound ( + 44% compared to intact ones), whereas the paradoxical sleep rebound was slightly decreased and delayed. When glucocorticoid action was replaced by an intramuscular injection of dexamethasone, a glucocorticoid receptor agonist, the sleep rebound was suppressed (-3% in slow-wave sleep and -37% in paradoxical sleep). Lastly, in a third series of experiments, plasma corticosterone concentration was evaluated at different times in rats immobilized for 1 h or 4 h. Corticosterone concentration was higher in stressed animals than in control ones (+92%) and returned to baseline 4 h earlier in animals immobilized for 1 h compared with those stressed for 4 h. Therefore, corticosterone is probably involved in the suppression of the sleep rebound after long immobilization periods since (i) dexamethasone suppressed the stress-induced sleep rebound, and (ii) corticosterone was elevated for a longer period in the 4 h immobilization group. It is concluded that the reparative sleep rebound is suppressed after long and intense stress periods and that a prolonged glucocorticoid secretion could be one of the factors responsible for this effect. This deleterious effect on sleep could impair normal recovery and quick adaptation to a new situation, and could participate in the development of stress-related pathologies in humans.     

Sleep deprivation in the rat: XV. Ambient temperature choice in paradoxical sleep-deprived rats.

Previous studies of total sleep deprivation (TSD) and paradoxical sleep deprivation (PSD) in the rat by the disk-over-water method have indicated that both produce changes in thermoregulation. In both kinds of deprivation, there was a progressive, large increase in heat production as indicated by measures of energy expenditure (EE). In TSD there was an initial increase in waking body temperature (Tb) followed by a later decrease; in PSD there was only a progressive decrease. The increases in heat production far in excess of heat storage indicated increased heat loss in both groups. Because the increase in Tb in TSD rats was supported by ambient temperature choices (Tch) in a thermal gradient that became progressively higher during deprivation, an increase in waking temperature setpoint (TSET) was indicated. Because the rats resorted to behavioral warming in spite of greatly increased thermogenesis, they must have had some failure to retain body heat. Prior to the present study, changes in TSET, had not been evaluated in PSD rats. Because they had not shown increases in Tb, PSD rats might not have an elevated TSET, which would indicate a functional difference between PS and nonrapid eye movement (NREM) sleep. Also, an evaluation of behavioral thermoregulation in PSD rats would clarify whether their Tb decline resulted from excessive heat loss or from a lowered TSET. To evaluate changes in heat flow and TSET, EE, Tb and Tch were measured in five PSD rats and their yoked control (PSC) rats. PSD rats showed progressive increases in EE and decreases in Tb as in the earlier PSD study; Tch rose progressively. PSC rats showed minimal changes in all three parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep deprivation effects on growth factor expression in neonatal rats: a potential role for BDNF in the mediation of delta power

The sleeping brain differs from the waking brain in its electrophysiological and molecular properties, including the expression of growth factors and immediate early genes (IEG). Sleep architecture and homeostatic regulation of sleep in neonates is distinct from that of adults. Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep deprivation is stressful to developing rats, we also investigated whether the increased levels of corticosterone would affect the expression of growth factors in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal days 16, 20, and 24, rats were subjected to sleep deprivation, maternal separation without sleep deprivation, sleep deprivation with 2 h recovery sleep, or no intervention. mRNA expression was quantified in the cortex and hippocampus. cFos was increased after sleep deprivation and was similar to control level after 2 h recovery sleep irrespective of age or brain region. BDNF was increased by sleep deprivation in the cortex at P20 and P24 and only at P24 in the hippocampus. FGF2 increased during recovery sleep at all ages in both brain regions. We conclude that cortical BDNF expression reflects the onset of adult sleep-homeostatic response, whereas the profile of expression of both growth factors suggests a trophic effect of mild sleep deprivation.     

Locomotor response to changes in food intake and ambient temperature in rats with hypothalamic lesions

The changes in wheel running activity in response to changes in the availability of food and to changes in ambient temperature were studied in rats made hypoactive by the placement of either ventrolateral or ventromedial electrolytic hypothalamic lesions. Even though wheel running activity was decreased by approximately 90% and 60% by ventrolateral and ventromedial lesions, respectively, the relative changes in this activity that occur when the feeding regimen is changed sequentially from restricted food intake to ad lib food intake to complete food deprivation, and when ambient temperature is decreased from 24.5°C to 19°C were not impaired. These data suggest that, although ventrolateral and ventromedial hypothalamic lesions decrease spontaneous locomotor activity, they do not impair the locomotor response to changes in environmental stimuli.     

Sleep deprivation in the rat: IV. Paradoxical sleep deprivation

Twelve rats were subjected to paradoxical sleep deprivation (PSD) by the disk apparatus. All PSD rats died or were sacrificed when death seemed imminent within 16-54 days. No anatomical cause of death was identified. All PSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (PSC) rats remained healthy. Since dehydration was ruled out and several measures indicated normal or accelerated use of nutrients, the food-weight changes in PSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all PSD rats increased EE, with mean levels reaching more than twice baseline values. All of these changes had been observed in rats deprived totally of sleep; the major difference was that they developed more slowly in PSD rats.     

The Effects on Subsequent Sleep of an Acute Restriction of Sleep Length

This experiment was designed to test the effects on subsequent sleep of a restriction in sleep length on the previous night. Eight male subjects were studied. After baseline recordings were made, sleep was restricted to either a period between 4-8 am or to a period between 6–8 am. On the night following the restriction of sleep the subjects retired at 11 pm and they were permitted to sleep ad lib in the morning. The restricted sleep periods resulted in differential sleep deprivation. Stages REM and 2 were markedly reduced whereas stages 3 and 4 showed little or no reduction in amount. There were significant reductions in sleep latencies and in the amount of lime spent in stages 0 and 1. The first 8 hrs of ad lib sleep following the 2 restricted sleep periods did not differ in any significant way from the 8 hrs of baseline sleep. When sleep was permitted to continue until the subjects awakened spontaneously, the sleep after the restriction of sleep to‘i hrs was significantly longer and displayed significantly more of stages REM and 2 when compared with the baseline ad lib sleep condition. The ad lib sleep period following the 4 hr condition showed similar changes although the differences were not statistically significant. The significant reductions in stages KEM and 2 during the restricted sleep periods were attributed to the effects of reduced steep length per se. The increases in sleep length and specifically the increases in stages REM and 2 during the ad lib sleep periods were attributed to a differential sleep “debt” accruing from restricted sleep length.     

Deviations in body fluids during fasting in rats: failure of ADH treatment and nonnutritive bulk in preventing the occurrence of plasma hypovolemia

During fasting rats initially exhibited a slight plasma hypervolemia followed by hypovolemia, with an accompanying increase in plasma osmolality, which became more severe as food deprivation continued. Urinary sodium, potassium and chloride concentrations were depressed with deprivation and this condition persisted through the six days of fasting examined. Urine osmotic pressure indicated a recovery trend by the fourth day of deprivation. This temporally coincided with a marked reduction in water consumption. In a second experiment Pitressin treatment increased urine osmolarity during four days of food deprivation, but urinary sodium and potassium concentrations were not changed nor was the plasma hypovolemia influenced. In the third experiment nonnutritive bulk in the form of Vaseline-cellulose mixture was ingested by both rats and gerbils during starvation. Water consumption and urine volume were decreased by such bulk ingestion, however, the urine remained dilute as compared with ad lib levels, and the plasma hypovolemia persisted.     

Absence of post-fast food compensation in the golden hamster (Mesocricetus auratus).

Ad lib food intakes and body weights were measured for hamsters fed one of 4 different diets. Animals were then placed on an intermittent starvation (IS) schedule in which food was available ad lib on alternate days only. Hamsters of both sexes showed little or no post-fast food compensation, i.e., after 24 hr of food deprivation their daily food intake was no greater than their daily intake during baseline testing. These animals lost a large percentage of their initial body weight and many of them died. Other hamsters restricted daily to half-day feeding periods that nearly coincided with the light (L) or dark (D) phases of the illumination cycle also failed to show food compensation; they generally ate no more during D- or L-periods that followed a half day of food deprivation than during D- or L-periods that succeeded a half day of ad lib feeding. These animals lost substantial portions of their initial body weight and many died. Hamsters refed after a 96-hr fast and an 18% loss in body weight also did not increase their food intake substantially above baseline values. In each of these experiments substantial portions of the body weight lost during starvation were not regained during extended ad lib refeeding regimens. These findings contrast strikingly with the behavior of rats tested concurrently; rats showed a dramatic post-fast hyperphagia, rapid recovery of body weight lost during starvation, and a reversal of the normal nocturnal feeding pattern when refeeding began during L-periods. Hamsters' nocturnal rhythms of eating and drinking were remarkably stable in the face of all the experimental manipulations. However, hamsters, as well as rats, were quite effective in compensating for changes in diet density; a 1:1 dilution of a liquid diet produced a prompt doubling in the volume of diet ingested. Impressive but less complete compensation was recorded when solid diets were diluted with inert substances (kaolin, cellulose). Hoarding and perhaps hibernation rather than compensation may have evolved as adaptations to periods of food scarcity. Noncompensation may be related to hamsters' nonresponsiveness to some signal of energy depletion. The possibility of lipogenesis being a rate-limiting step is considered. The desirability of adequate field data as a prerequisite to laboratory analysis of feeding behavior is emphasized.     

Schedule and quinine induced deprivation in feeding and refeeding

Twenty female albino rats were adapted to either 0 or 23 hr of food deprivation. Half of each group was then fed 0.125% quinine sulfate adulterated diet for seven days. Following the quinine feeding, ad lib feeding (refeeding) was instituted for 14 days. Several conclusions were drawn from the results: (1) rats on a deprivation schedule fail to show a predicted change to regulation on the basis of taste rather than calories; (2) rats on food deprivation actually increase their relative intake of water; (3) refeeding after a deprivation schedule does not lead to depression of initial intake below normal, but otherwise the process of recovery follows the same course as after total starvation.     

Total sleep deprivation increases extracellular serotonin in the rat hippocampus

Sleep deprivation exerts antidepressant effects after only one night of deprivation, demonstrating that a rapid antidepressant response is possible. In this report we tested the hypothesis that total sleep deprivation induces an increase in extracellular serotonin (5-HT) levels in the hippocampus, a structure that has been proposed repeatedly to play a role in the pathophysiology of depression. Sleep deprivation was performed using the disk-over-water method. Extracellular levels of 5-HT were determined in 3 h periods with microdialysis and measured by high performance liquid chromatography coupled with electrochemical detection. Sleep deprivation induced an increase in 5-HT levels during the sleep deprivation day. During an additional sleep recovery day, 5-HT remained elevated even though rats displayed normal amounts of sleep. Stimulus control rats, which had been allowed to sleep, did not experience a significant increased in 5-HT levels, though they were exposed to a stressful situation similar to slee-deprived rats. These results are consistent with a role of 5-HT in the antidepressant effects of sleep deprivation.     

Hypophysectomy in monosodium glutamate-pretreated rats suppresses paradoxical sleep rebound

Control untreated and pretreated female rats at birth with 10 injections of monosodium glutamate (MSG, 4 mg/g b. wt.) were hypophysectomized (HYPX) at 45-60 days of age and their sleep-waking cycle continuously registered. In control rats, hypophysectomy was followed by a 35.7% decrease in paradoxical sleep (PS) duration while it has no effect on the sleep of MSG-treated rats. After 24 h of PS deprivation, there was a normal immediate rebound of PS in the control HYPX and MSG rats while there was no significant rebound in the HYPX-MSG-treated rats. It is concluded that neuropeptides from arcuate nucleus and hypophysis are involved in a PS rebound mechanism.