Jaber Danguir

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.

Chronic intracerebroventricular infusion of insulin causes selective increase of slow wave sleep in rats

Sleep patterns were continuously recorded in rats receiving chronic intracerebroventricular (i.c.v.) infusions of insulin. The i.c.v. administration of insulin resulted in a selective increase (25%) of the daily duration of slow wave sleep (SWS), whereas the duration of paradoxical sleep (PS) remained unchanged. The neutralization of peripheral and/or central insulin by means of continuous intravenous or i.c.v. infusions of anti-insulin serum brought about a selective decrease of SWS, whereas PS remained unchanged. The present findings are discussed with regard to the present knowledge of the origin and the role of brain insulin.

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.

Apomorphine and haloperidol effects on striatal 3H-dopamine release in anesthetized, awake restrained and freely moving rats

The ability of apomorphine (APO) and haloperidol (HAL) to affect the spontaneous release of newly synthesized 3H-DA in the striatum was studied in halothane anesthetized, gallamine paralyzed, awake restrained and freely moving rats. The striatum was continuously superfused through a push-pull cannula with a physiological medium enriched in 3H-tyrosine. Basal levels of 3H-DA release were different in the four experimental models: highest in halothane anesthetized rats, intermediate in awake restrained and gallamine treated rats and lowest in freely moving rats. In all experimental models IV or SC injection of APO (1 mg/kg) inhibited the release of 3H-DA (30-50%) from 15 to 90 min following its administration. In awake restrained and freely moving rats, stereotyped behaviour was observed for one hour following the APO injection. In halothane anesthetized rats the inhibitory effect of APO on 3H-DA release was prevented by pretreatment with HAL (2 mg/kg IV). Injection of HAL (2 mg/kg IV or SC) failed to enhance the release of 3H-DA in anesthetized and awake restrained rats, whilst a long-lasting increase in 3H-DA release was observed in gallamine treated and freely moving animals (55% and 120% respectively). However, catalepsy was observed in both restrained and freely moving rats. It is concluded that the modifications of 3H-DA release produced by HAL but not those produced by APO are dependent on the experimental model used, a fact possibly related to the different sites of action of these two drugs.

Sleep and feeding patterns in the ventromedial hypothalamic lesioned rat.

Abstract Sleep and feeding patterns were recorded in Ventromedial Hypothalamic (VMH) lesioned rats during 10 to 15 consecutive days. During the dynamic phase of hyperphagia, daily Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) were significantly increased compared to normal rats. These increases were exclusively due to a greater duration of SWS and PS episodes and a higher number of PS episodes during the dark period of the day. During the static phase, sleep amounts returned, as did food intake, to normal values but the equal circadian sleep distribution observed during the dynamic phase persisted. During the dynamic phase, the size of a meal was highly correlated with sleep events within the intermeal interval (IMI) preceding it, and only weakly correlated with sleep within the subsequent IMI. Unlike normal rats, there were no significant variations in deprivation and satiety ratios throughout the nycthemeron. These findings suggest that in VMH lesioned rats, physiological parameters determining sleep and feeding are perhaps more important than ecological ones. In addition, possible causative relations and common underlying factors between sleep and feeding are discussed.

Food intake in rats is increased by intracerebroventricular infusion of the somatostatin analogue SMS 201–995 and is decreased by somatostatin antiserum

The chronic intracerebroventricular infusion of the somatostatin analogue SMS 201-995 resulted in a significant increase in daily food intake which was accompanied by an unexpected body weight loss. The neutralisation of central somatostatin using a specific somatostatin antiserum resulted in a significant decrease in daily food intake. These results suggest that endogenous somatostatin in the brain can drive feeding behavior and alter body weight.

Somatostatin antiserum blocks carbachol-induced increase of paradoxical sleep in the rat

Injection of carbachol into the nucleus tractus solitarius (NTS) produced an increase of paradoxical sleep (PS). When somatostatin antiserum (SRIF-AS) was infused continuously following carbachol injection, the increase in PS was blocked. These results suggest that carbachol-induced increase in PS is mediated by somatostatin. In addition, they confirm the role of somatostatin in the generation of PS.

Sleep deficits in diabetic rats: restoration following chronic intravenous or intracerebroventricular infusions of insulin

The role of insulin in sleep was investigated in the present study by using streptozotocin-induced insulin deficiency in rats. Our previous studies showed a selective increase in the daily duration of slow wave sleep following either peripheral or central administration of insulin in normal rats. We now report sleep deficits following the pharmacological destruction of pancreatic B insulin-producing cells. The daily duration of both slow wave sleep (SWS) and paradoxical sleep (PS) were decreased on the third day following the injection of streptozotocin. However, only SWS remained lower than the control levels two weeks after the treatment whereas PS returned to normal values. The continuous intravenous infusion of exogenous insulin (2 IU per 24 hr) brought about a selective restoration of SWS in insulin-deficient and hyposomniac rats. A dose-dependent restoration of SWS was also observed when exogenous insulin was continuously administered intracerebroventricularly in streptozotocin-treated diabetic rats. Although the mechanism of the induction of sleep by insulin remains to be elucidated, these results clearly support its hypnogenic properties. A possible direct action of insulin on brain cells is suggested.

LCEC monitoring of 5-hydroxyindolic compounds in the cerebrospinal fluid of the rat related to sleep and feeding

A new technique which allows for both the chronic withdrawal of CSF and continuous recording of EEG sleep patterns and food intake in the freely moving rat is described. Liquid chromatography with electrochemical detection (LCEC) was used for the direct assay of tryptophan metabolites in the CSF. Both 5-hydroxyindolacetic acid (5-HIAA) and 5-hydroxytryptophan (5-HTP) were easily detectable. However, serotonin (5-HT) levels were relatively low and 5-hydroxytryptophol (5-HTPhol) and N-methylserotonin (N-Me-5HT) were undetectable in several cases. The continuous monitoring of 5-HIAA and 5-HTP indicated stable values throughout the 3-hr experiments during which no food or small meals were consumed. In the rat which consumed a large meal, both 5-HIAA and 5-HTP significantly increased following that meal. This increase in metabolites may be the result of an increased availability of tryptophan to the brain as a result of the meal. Although this study is preliminary, the described technique can provide further information about the possible relationship between behavioral (sleep and/or feeding) changes and the concomitant neurochemical fluctuations.

Lack of reacquisition in learned taste aversions

Following ingestion of either water (Experiment 1) or saccharin (Experiment 2), experimental groups of rats were poisoned with lithium chloride and acquired an aversion to the ingested fluid. This aversion gradually extinguished and, in both experiments, was not reacquired when fluid intake was again followed by poisoning. These results are in marked contrast to usual findings of very rapid relearning following extinction with conditioning preparations other than taste-aversion learning.