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S Nicolaidis

Publications and source records attributed to S Nicolaidis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolic action of neuropeptide Y in relation to its effect on feeding.

Because energy homeostasis depends on a continuous balance between food intake, energy expenditure, and energy storage, it was expected that neuropeptide Y (NPY) could act not only on food intake but also on metabolic parameters. Using an original calorimetric device that allows the computation of the background metabolism (energy expenditure free from the cost of locomotor activity), we assessed the effect of a microinjection of NPY upon the quantitative (background metabolism, thermic effect of food) and qualitative (respiratory quotient) components of energy metabolism. NPY was injected into the juxtafornical hypothalamus at a dose that promotes feeding behavior (1 microg/0.5 microL) and enhances locomotor activity. Although total metabolism was increased proportionally to locomotion, no effect of NPY on background metabolism was observed when no food was available. Only following a calibrated meal given 30 min after the microinjection did NPY induce a delayed decrease in respiratory quotient whereas the postprandial background metabolism remained unaffected. In conclusion, only the new-generation calorimeters can show that the NPY-induced rise in overall metabolic rate is entirely accounted for by the unavoidable enhancement in locomotor activity and that the only metabolic effect of NPY is the delayed postprandial respiratory quotient decrease, suggesting a postabsorptive orientation toward more lipid utilization.

Animals↗
PubMed1997

Aversion-preference patterns in amino acid- or protein-deficient rats: a comparison with previously reported responses to thiamin-deficient diets.

The purpose of the present experiments was to extend previous data on the strategy used by adult rats to select feed appropriately when faced with diets devoid of protein or an essential amino acid (EAA), and to compare this strategy with that used when facing vitamin (thiamin) deficiency. Rats fed on either balanced or deficient (EAA or protein) diets were offered a choice between a novel deficient and a familiar (deficient or corrected) diet and their choice was monitored. It was shown that protein- and EAA-deficient rats acquired an aversion for their corresponding familiar devoid diet, which by itself promoted a neophilia for the novel diet. This neophilia was not non-specific because protein-deficient rats facing a choice between a protein-devoid and an EAA-devoid diet did exhibit neophilia but only in the short term (less than 5 h), and then switched to a preference for the familiar protein-devoid diet. These results show that, in contrast to the case of vitamin deficiency, the protein- or EAA-devoid diet-induced neophilia can be rapidly reversed if the novel feed happens to be more deleterious than the familiar, inappropriate one. This behaviour suggests the existence of sensitive mechanisms able to reveal within a short time the EAA inadequacy of the ingested feed and to adapt the choice for the most appropriate feeds more promptly than in the face of thiamin deficiency. Thus it appears that balancing EAA is more urgent than balancing thiamin.

Animal Feed↗
PubMed1996

Neuronal responses to iontophoretically applied angiotensin II, losartan and aldosterone, as well as gustatory stimuli, in non-anesthetized control and desoxycorticosterone acetate-pretreated rats.

The neuronal mechanism of the sodium appetite initiated in rats by priming with a mineralocorticoid (desoxycorticosterone acetate (DOCA)) treatment and subsequent central angiotensin II (Ang II) was investigated using electrophysiological-iontophoretic techniques and sapid salt stimulation of the tongue in non-anesthetized restrained, DOCA-pretreated (0.5 mg/day s.c. for 3 days) or non-pretreated male Wistar rats. The rats were trained to drink water and a 1.6% NaCl solution while their heads were painlessly held in a stereotaxic apparatus with an attachment fixed to the skull. A total of 634 neurons (375 in non-pretreated and 259 in DOCA-pretreated rats) were recorded in the medial septum and median preoptic area during iontophoretic application of Ang II, aldosterone or losartan, or tongue application of the salty solution or water. Of the 151 neurons recorded in control rats during the application of the solutions on the tongue, one (0.7%) was found specifically excited and 16 (10.6%) inhibited by the sapid sodium. Similarly, of the 110 neurons tested in the DOCA-pretreated rats, 5 (4.5%) were found specifically excited and 8 (7.3%) inhibited by the sapid sodium. The number of neurons responding to the iontophoretically applied agents was not significantly changed by the DOCA pretreatment. Thus, the DOCA pretreatment significantly increased the number of preoptic neurons that were specifically excited by a salty solution applied on the tongue. These results suggest that hormonally induced changes in the gustatory responsiveness of ventral forebrain neurons may be part of the sequence that alters the hedonic valence of NaCl during sodium appetite.

Aldosterone↗
PubMed1996

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.

Animals↗
PubMed1996

Melanin-concentrating hormone is a potent anorectic peptide regulated by food-deprivation and glucopenia in the rat.

Melanin-concentrating hormone is a cyclic nonadecapeptide that is produced almost exclusively in neurons of the lateral hypothalamus and sub zona incerta areas while fibers are widespread in the rat brain. Such a localization strongly suggests that this peptide might participate as neurotransmitter/neuromodulator in the control of feeding behavior. In this study we examined first the influence of rat melanin-concentrating hormone on feeding behavior at different times either in the light or in the dark period (light off at 18.00 h) of the day in fed Wistar rats. Intracerebroventricular injection of rat melanin-concentrating hormone (1-100 ng per rat) at 18.00 h reduced food consumption as early as 2 h after injection and for the next 24 h. In addition, similar anorectic effect was noted after bilateral administration of 1 ng melanin-concentrating hormone into the lateral hypothalamic area at 11.30 h but not at 16.30 h. These findings strongly suggest that rat melanin-concentrating hormone may exert inhibitory control over food intake behavior depending on the circadian rhythm. Second, we investigated the modifications induced by food deprivation/refeeding on melanin-concentrating hormone messenger RNA levels in Wistar rats. Total RNA was isolated from whole hypothalamic dissections and the contents of melanin-concentrating hormone messenger RNA, beta-actin messenger RNA (taken as sample control) and neuropeptide Y messenger RNA (taken as control of food-deprivation paradigms) were assessed by using northern blotting. The time-course of messenger RNA expression was determined in groups of rats deprived for 24, 48 and 72 h and revealed a three-fold induction of melanin-concentrating hormone messenger RNA by 24 and 48 h, with reduced increase at 72 h. As expected, the same treatment led to a three-fold increase in neuropeptide Y messenger RNA content by 48 and 72 h. Refeeding groups of animals for up to 72 h after 24 h of food deprivation resulted in full restoration of melanin-concentrating hormone messenger RNA levels by 24 h. Strikingly, a large range of variations in melanin-concentrating hormone messenger RNA content between individuals was observed in food-deprived versus controls or refed rats suggesting that genetic or environmental factors may alter response in melanin-concentrating hormone gene activity after food deprivation. Finally, we investigated the effects of short-term glucoprivation induced by intraperitoneal administration of either 2-deoxy-D-glucose or insulin on melanin-concentrating hormone messenger RNA expression. A transitory increase in melanin-concentrating hormone messenger RNA content was noted 1 h after 2-deoxy-D-glucose injection while melanin-concentrating hormone messenger RNA levels rose two-fold only 5 h after insulin treatment. These results indicate that 2-deoxy-D-glucose and insulin activate melanin-concentrating hormone gene expression through likely distinct regulatory pathways.

Animals↗
PubMed1996

Rebalancing essential amino acids intake by self-selection in the rat.

The purpose of the present study was to assess whether rats are capable of selecting the right proportions of two diets that are individually inappropriate in terms of essential amino acid composition to satisfy their amino acid requirements. Rats were offered a choice of one protein-free regimen and another devoid of only one essential amino acid (either threonine or isoleucine) set up in such a way as to provide amino acid balance if they were consumed in 1/3 and 2/3 proportions respectively. Preliminary experiments had established that all our diets were aversive by themselves except for the 60 g casein/kg diet. Rats did reach almost the necessary proportion with, according to published standards (National Research Council, 1978), some excess in isoleucine intake. In addition, given access to two aversive diets that were each nutritionally inadequate, rats showed no aversion and gained body weight when they had the opportunity to consume both of them. Beyond the capacity that rats have of rebalancing their micronutrient intake, the present experiment brings out the idea that the imbalance-induced aversion:preference ratio may be completely upset when this omnivore has access to more than one feed.

Amino Acids↗
PubMed1995

Parallel metabolic and feeding responses to lateral hypothalamic stimulation.

Energy metabolism and food intake effect each other. Many studies demonstrated that the lateral hypothalamus (LH) participates in the control of both feeding behavior and energy metabolism. We assessed the effect of a bipolar near threshold feeding eliciting electrical stimulation of the LH first on the feeding response and then on the background metabolism (metabolism free from the part due to locomotion) and respiratory quotient (RQ), on Wistar male rats, during either the light or the dark phase of the nycthemeron. LH stimulation resulted in a delayed and rather long increase in background metabolism that was more dramatic during the light phase. This metabolic response paralleled the delayed feeding response (more than 10 min) we obtained during behavioral tests. The increase in energy production was sustained by release of energy substrates from the endogenous stores, and this showed a circadian dependence. Mainly carbohydrates (rise in RQ) were used during the light phase stimulation whereas lipids (decrease in RQ) were released in the dark phase.

Analysis of Variance↗
PubMed1995

Spontaneous feeding-related monoamine changes in rostromedial hypothalamus of the obese Zucker rat: a microdialysis study.

Using microdialysis in freely moving rats, we have been able to observe changes in monoamines from the ventromedial and paraventricular hypothalamic nuclei before, during, and after spontaneous feeding. Because the genetically obese Zucker rat shows abnormalities related both to feeding and monoamines, it was of interest to investigate possible particularities in the monoaminergic variations around spontaneous feeding. The profile of changes in Zucker rats was grossly similar to that of Wistar rats: increases in 5-hydroxy-tryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and dopamine (DA), and decrease in dihydroxyphenylacetic acid (DOPAC). However, the release in monoamines (5-HT and DA) was more dramatic and longer-lasting than in Wistar rats, while the changes in the metabolites were proportionnally less pronounced. This suggests that high concentrations of these feeding-related amines are released and remain in the synaptic cleft of the obese rat, possibly because they are required in larger amounts to bring about satiety. The hyperphagia of the obese Zucker rat may therefore be the result of a resistance to these prandially released satiety-promoting neurosubstances.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of mefenorex on 5-HT release: studies in vitro on rat hypothalamic slices and in vivo by microdialysis.

Mefenorex, used for 20 years as an anorexic drug, has not been studied so far with regard to its central mechanism of action, although its chemical structure suggests a serotonergic mechanism. In the present study, the effect of mefenorex on serotonin (5-HT) release was investigated both in vitro, on rat hypothalamic slices and in vivo, using microdialysis in the paraventricular (PVN)-ventromedian (VMH) hypothalamic area while mefenorex was applied locally by means of counterdialysis. In vitro, mefenorex increased the spontaneous release of 3H 5-HT from hypothalamic slices but not the electrically evoked release. This suggests a 5-HT releasing action of mefenorex not mediated through the terminal autoreceptor. The in vivo study confirmed the enhanced release and provided additional information. The delayed and modest increase of the 5-HT intracellular metabolite 5-HIAA may be indicative of an inhibition of reuptake. The dopaminergic system was also, but more modestly, activated by mefenorex. The increase in 5-HT release together with the inhibition of its reuptake may represent the main mechanism of action of mefenorex, and the secondary activation of the dopaminergic system may contribute in its anorexigenic effect at the level of the PVN-VMH area.

Amphetamines↗
PubMed1995

Dynamic changes in hypothalamic monoamines during sleep/wake cycles assessed by parallel EEG and microdialysis in the rat.

Monoaminergic changes during sleep/wake cycles were investigated in the rostral hypothalamic areas since feeding, metabolism and sleep were shown to be causally related. Thus, the microdialysis probe was located stereotaxically in the ventromedial and paraventricular nuclei and cemented together with cortical electrodes for EEG sleep recordings. The monoaminergic changes were extensively investigated. Sampling of dialysates over six minutes in freely behaving rats showed an increase in 5-HT and its metabolite 5-HIAA during wakefulness. DOPAC rose during PS. The two other monoamines, DA and NA, remained unchanged. It appears that this method of investigation, extended in the future to other candidate areas and other dialysable substances, may provide us with a dynamic picture that characterizes the sleep/wake cycle.

Journal Article↗
PubMed1994

Resistance of the obese Zucker rat to insulin-induced feeding and to satiety induced by coinfusion of insulin and glucose.

In normal rats, hypoglycemic doses of intravenous insulin bring about glucoprivic feeding but the same doses of insulin inhibit feeding when combined with doses of glucose that prevent hypoglycemia. In this study, these effects were compared between obese Zucker rats (fa-fa), known to present several abnormalities related to insulin, and normal Wistar rats by infusion of insulin (1 IU over 1 h), insulin plus glucose (5.1 g over 2 h) or vehicle. Feeding patterns and microstructure were automatically monitored. Contrary to its effect in the normal rats, insulin infusion did not enhance feeding in the Zucker rats but rather slightly decreased total food intake and meal duration. The insulin plus glucose infusion produced a total anorexia in normal rats but only a partial reduction in total food intake and meal duration was observed in Zucker rats. The impaired feeding effect of insulin in the Zucker rat may be related to its peripheral resistance to insulin which prevents a severe hypoglycemia and therefore glucoprivic feeding. The lack of inhibition of feeding when both insulin and glucose are infused may account for the well-known delayed satiation and large meals in the Zucker rats, possibly involving impaired hypothalamic action of insulin.

Animals↗
PubMed1994

Serotoninergic modulation of sodium appetite in the rat.

There are two mechanisms leading to an enhancement of salt intake: one is induced by a sodium deficit and the other is need-free. The serotonin involvement in need-induced and/or need-free sodium appetite is interesting to consider because related drugs are already used against another cardiovascular risk factor, obesity. The effect of dexfenfluramine (1.5 or 3 mg/kg), an anorectic drug enhancing 5-HT transmission, and of metergoline (2 or 4 mg/kg), a 5-HT antagonist, was assessed in need-induced (depletion-induced), subsequent need-free, and spontaneous sodium appetite. Dexfenfluramine (3 mg/kg) decreased by 75% to 90% the depletion-induced intake of an aversive 3% NaCl solution, as well as the spontaneous intake of a less aversive 1.8% NaCl solution. Water intake was not diminished under these conditions. Metergoline significantly increased salt intake in need-free conditions in rats with either a history of three previous depletions or not. These results confirm the involvement of serotonin in sodium appetite and extend this involvement to both need-induced (natriorexis) and need-free (natriophilia) conditions. The metergoline experiments also suggest that 5-HT exerts a tonic inhibition on salt intake.

Animals↗
PubMed1994

Tonic neuronal inhibition by AII revealed by iontophoretic application of Losartan, a specific antagonist of AII type-1 receptors.

Short-term low-dose mineralocorticoid pretreatment enhances subsequent neuronal activity in the medial septum/preoptic region and in the stria terminalis/posterior amygdala of urethane anaesthetised male Wistar rats and sensitises these neurons to angiotensin II (AII). We have investigated the effect of iontophoretic application of Losartan, a specific nonpeptidergic AII type-1 receptor antagonist, on the background activity of spontaneously active neurons in these regions using a seven-barrelled microiontophoretic electrode sealed to a recording electrode. The influence of Losartan on the effects of iontophoretically applied AII in deoxycorticosterone acetate (DOCA) pretreated and nonpretreated rats was also investigated. Iontophoretically applied Losartan was observed to block the excitatory effect of AII in some neurons. In other spontaneously active neurons Losartan was seen to stimulate (or inhibit) immediately, this effect being greater in nonpretreated than in DOCA pretreated rats. Losartan was also observed to provoke persistent excitation of some spontaneously active neurons only in the nonpretreated rats. These results suggest that there exists a tonic inhibition by AII on the neurons in this area of the forebrain and that there may exist at least two subtypes of the AII type-1 receptor.

Aldosterone↗
PubMed1994

Insulin and glucose-induced changes in feeding and medial hypothalamic monoamines revealed by microdialysis in rats.

Microdialysis from the ventromedian (VMH) and paraventricular (PVN) regions and simultaneous infusion of insulin alone (orexigenic) or with glucose (anorexigenic) was performed in the free-feeding rat. Intravenous insulin infusion (1 IU in 1 ml over 1 h) resulted in the expected glucoprivic feeding and a decrease in dopamine (DA) and serotonin (5-hydroxytryptamine [5-HT]) with an increase in their respective metabolites, dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolacetic acid (5-HIAA). These data are quite different from those observed in spontaneous ad lib feeding: increase in DA, 5-HT and 5-HIAA and decrease in DOPAC. These last changes were not superimposed on insulin effects when insulin-induced meals occurred. When food was not available, insulin infusion induced the same changes except an increase in DA levels which could probably be ascribed to stress. When insulin was infused together with a sufficient amount of glucose to prevent hypoglycemia, we observed the usual anorexigenic effect. Although this treatment had an effect on induced-feeding opposite to that following insulin alone, the changes in hypothalamic monoamines were similar. The only consistent overall change is finally the rise in 5-HIAA found in both spontaneous and induced feeding conditions. These data suggest that monoaminergic changes in the VMH and PVN are not directly implicated in the control of feeding but they rather reflect metabolic events that accompany this behavior.

Animals↗
PubMed1993

Basal and hyperinsulinemia-induced immunoreactive hypothalamic insulin changes in lean and genetically obese Zucker rats revealed by microdialysis.

Lean and genetically obese Zucker rats were implanted with permanent intravenous catheters and a guide cannula was aimed at the region of the ventromedial (VMH) and paraventricular (PVN) nuclei to measure immunoreactive insulin collected by means of microdialysis. Preliminary experiments assessed the validity of a novel assay of insulin in microdialysates by a sensitized radioimmunoassay technique. This method was then used to measure basal levels of insulin and those induced by i.v. infusion of 0.5 U of insulin over 30 min in both lean and obese rats. Basal hypothalamic immunoreactive insulin levels were lower in the obese rats than in the lean Zucker rats. When insulin was infused i.v. for 30 min, hypothalamic immunoreactive insulin showed an increase in the 30-60 min sample, which was twice as great in the obese rats. Two facts suggest that the insulin found in the microdialysates was of cerebral, not vascular origin: the short latency in the response and the finding that the response was greater in obese rats.

Animals↗
PubMed1993

Nonamphetamine awakening agent modafinil induces feeding changes in the rat.

In rats, modafinil, an alpha1 adrenergic receptor dependent, that has been shown to increase wakefulness without subsequent rebound effect, decreases feeding and reduces body weight. However, modafinil does not show a monotonic dose-related decrease in food intake. The dose-response curve for modafinil is U-shaped; feeding decreases after doses of 20 and 40 mg/kg, but no effects were seen after doses of 10 and 80 mg/kg. When feeding is resumed, no compensatory effect is seen, and body weight remains lower during the 24-h session. The drinking-to-feeding ratio remains unchanged, showing that modafinil has no effect on water intake. These results are discussed with reference to the possible mechanisms underlying the relation between sleep, feeding, and metabolism.

Adrenergic alpha-Agonists↗
PubMed1993

Blood pressure effects of iontophoretically applied bioactive hormones in the anterior forebrain of the rat.

In the course of electrophysiological investigations using iontophoresis, we observed that in specific regions of the forebrain even these minute applications of peptide and steroid hormones can influence systemic blood pressure. In urethan-anesthetized male Wistar rats, with a catheter in the femoral artery, iontophoretic application of the peptide hormones angiotensin II (ANG II), vasopressin (AVP), and atrial natriuretic peptide (ANP) and the steroid hormone aldosterone (ALDO) was effective at locations in the midline septum, the triangularis nucleus of the septum, and the subfornical organ (SFO). Increases in blood pressure (of up to 15 mmHg) were observed after ANG II and AVP, decreases after ALDO, and either an increase or a decrease, depending on the location, after ANP. There was no clear evidence of an antagonistic effect of ANP on ANG II-induced neuronal or blood pressure responses. In addition to demonstrating the potency of these hormones even when they are restricted to tiny volumes of tissue, the present results demonstrate that the medial ventral region of the anterior forebrain may be included in the same baroreceptive circuit as the SFO (and organ vasculosum of the lamina terminalis) and hence be involved in the regulation of blood volume and perhaps in the sensing of and corrective responses to extracellular thirst.

Aldosterone↗