Biomedical subjects

S Nicolaidis

Publications and source records attributed to S Nicolaidis.

At least 19 recordsLinked to original sources

PubMed2001

Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats.

The role of brain amines in mediating the effects of the wake-promoting agent modafinil, used in the treatment of sleepiness associated with narcolepsy is still uncertain. Therefore we studied the effects of modafinil on extracellular serotonin (5-HT), dopamine (DA) and noradrenaline (NA), in rat prefrontal cortex and in the medial hypothalamus area. Modafinil (128 mg/kg i.p.) significantly increased waking in the first 4 h of EEG sleep recording. This cortical and behavioral activation was associated with an initial increase in extracellular 5-HT, DA and NA during the first 60 min following modafinil administration. In the prefrontal cortex, 5-HT release remained high for 3 h after modafinil administration. In contrast, in the hypothalamus, only NA release was enhanced while DA and 5-HT levels remained low. In a first step, modafinil may generate waking partly via cortical monoamine release, particularly DA and 5-HT, and also hypothalamic NA. In a second step, maintenance of waking might depend on hypothalamic NA.

Animals↗

PubMed2001

Extracellular serotonin variations during vigilance states in the preoptic area of rats: a microdialysis study.

Numerous studies have shown that serotonergic transmission decreases from waking (W) to slow wave sleep (SWS) to paradoxical sleep (PS), suggesting an active role of serotonin (5-HT) in W but not in sleep. Conversely, the inhibition of 5-HT activity produces insomnia. This insomnia can be reversed by injections of 5-hydroxytryptophan in the preoptic area (POA), suggesting that 5-HT is necessary in this cerebral structure for sleep. Using microdialysis, we studied, 5-HT variations in the POA of rats in relation to vigilance states. 5-HT levels were higher during W than during during SWS and PS. 5-HT increased just before the rats fell asleep and then decreased during sleep. A decreased 5-HT transmission was also observed from SWS to PS. These data document a positive correlation between 5-HT levels in POA and wakefulness. Moreover, these observations are in favour of a permissive role of 5-HT in the POA during PS. A comparison between the POA and the prefrontal cortex in the sleep-wake cycle is discussed.

Animals↗

PubMed2001

A potential role of central insulin in learning and memory related to feeding.

1. Hypothalamic insulin (HI) is well known for its role in feeding regulation. In addition, its concentration is modified in response to meals. Recent studies suggest that brain insulin participates in memory processes, possibly through stimulation by glucose. 2. The present microdialysis study focused on local in vivo regulation of HI by glucose and on the effects of aging on HI, since aging is characterized by deterioration of memory, body weight regulation, and central glucose utilization. Glucose (8 mM) infused for 5 min increased extracellular HI levels rapidly, by 4.6-fold, and cerebellar insulin levels by 0.4-fold only, suggesting a specific area-dependent regulation of HI by glucose. Neither insulinemia nor glycemia were affected, suggesting a central mechanism. The same dose of glucose induced a modest (0.4-fold), delayed (45 min) increase in hypothalamic serotonin, suggesting that the effect of glucose on HI is independent of a previously defined local serotonin-induced insulin release. HI levels in old normal weight rats were half the levels of young rats. In genetically old obese (fa/fa) Zucker rats, HI concentration was 30% of that in young normal rats, suggesting a deterioration of HI availability when aging and obesity are combined. 3. The above results, in line with recent considerations on a potential role of central insulin in learning and memory, suggest particular effects of HI on feeding and memory and probably on a specific "memory for food."

Age Factors↗

PubMed2001

Effects of pure macronutrient ingestion on plasma tryptophan and large neutral amino acids.

The role of tryptophan and its competitor large neutral amino acids, proposed earlier for serotonin synthesis following carbohydrate or protein ingestion, was reassessed in relation to a recent study investigating serotonin release, including the so far unknown effects of fats. In the present study, meals of either carbohydrates, casein, or lard, were supplied to rats for 30 min and blood samples collected every 15 min to follow the changes in plasma large neutral amino acids. In response to carbohydrates, amino acid levels fell and the ratio tryptophan over sum of other amino acids increased. Following casein ingestion, all amino acids were enhanced, tryptophan somewhat less, leading to a decreased ratio. The lard meal induced a slight decrease in some amino acids while the ratio remained constant. Only in response to casein, and partly to carbohydrates, did a consistent relation appear between the previously observed serotonin changes and the ratio. These data suggest that a relationship between the ratio and the previously observed serotonin changes is not always encountered because the release is not obligatorily coupled to synthesis and is subject to behavioral influences. It remains that serotonin release is affected by the composition of the meal through peripheral metabolic mechanisms.

Amino Acids, Neutral↗

PubMed2001

Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight.

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.

Animals↗

PubMed2001

[Variations of hypothalamic and cortical prostaglandins and monoamines reveal transitions in arousal states: microdialysis study in the rat].

Brain microdialysis coupled with EEG recording allowed us to track dynamic neurochemical changes every 3 or 6 minutes in relation to sleep/wake cycles. We chose to investigate prostaglandins (PG) and monoamines (catecholamines, serotonin and metabolites) because of their respective role in the states of vigilance, mainly suggested by pharmacological approaches, and because of the known interactions between PGs and monoamines. We focused on the paraventricular and ventromedial nuclei of the hypothalamus for their involvement in the relationships between feeding, metabolic rate and sleep, and the prefrontal cortex for its role in vigilance. These studies revealed a few changes in prostaglandin or monoamine levels as a function of a given state of vigilance. In particular, serotonin levels were higher during wakefulness than during sleep in both hypothalamus and cortex. Both hypothalamic and cortical PGE2 levels were higher during wakefulness than during slow wave sleep and still higher during paradoxical sleep in the cortex. Cortical PGD2 showed an exactly reverse profile of PGE2. These changes are in agreement with the described awaking action of PGE2 and with the hypnogenic action of PGD2. Our most informative findings were the sequential changes around transitions from one state to another that allow to predict the moment of onset of both sleep and wakefulness. Both in hypothalamus and in cortex, ondulatory patterns of PGE2 were encountered around the transitions between states. PGE2 was high in the middle of wakefulness, then regularly dropped announcing the occurrence of sleep, where the drop persisted before giving place to a rise in prediction to the next period of wakefulness. A similar profile was also observed for cortical serotonin, but its low levels reached a plateau during sleep. Cortical dopamine levels showed sudden and dramatic drops during short periods of wakefulness closely surrounding slow wave sleep. In some instances, as in the case of PGE2, similar profiles of variations could be found both in the hypothalamus and cortex. But in most cases, different and even opposite profiles were encountered in those two structures. Interestingly, in some instances, the pattern of changes in both prostaglandins and monoamines were similar, as for example between hypothalamic PGE2 and dopamine as well as between cortical PGE2 and serotonin. These similarities support the idea of the suggested interaction between prostaglandins and monoamines, in particular concerning their involvement in the regulation of sleep/wake cycles.

Animals↗

PubMed2000

Intracerebroventricular injection of murine leptin enhances the postprandial metabolic rate in the rat.

Energy balance is achieved by means of a concomitant control of both food intake and energy expenditure. Leptin, synthesized in the adipose tissue, acts on brain structures and lowers body weight by inhibiting food intake and in parallel by enhancing energy expenditure i.e. metabolism or one of its components. Recording distinctly these components allowed us to assess the effect of an acute intracerebroventricular injection of leptin on both feeding pattern and background metabolism (i.e. energy expenditure free from the part of locomotor activity), respiratory quotient, feeding-related metabolism and locomotor activity-related metabolism. Leptin injection to Sprague-Dawley male rats induced an inhibition of feeding that began 90 min after the treatment and lasted 1 h before to return to the control feeding pattern level. Considering this late behavioral effect, it appeared that leptin may act during the postprandial period so that we recorded the different metabolic parameters following a 3 g calibrated meal itself preceded by leptin vs. artificial cerebrospinal fluid injection. Postprandial respiratory quotient was rapidly lowered in leptin-treated animals and subsequent background metabolism increased for 6 h. Thus it appeared that leptin increased the duration of the postprandial metabolic rate via the recruitment of endogenous fat stores. Enhancement in the thermic effect of food may be the reason for feeding behavior inhibition to be delayed.

Animals↗

PubMed2000

Neuromodulation of the prefrontal cortex during sleep: a microdialysis study in rats.

To test the hypothesis that biogenic amines of the prefrontal cortex are involved in state-dependent cortical and behavioural activation, changes in extracellular levels of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) were determined during the sleep-wake cycle in freely moving rats using microdialysis probes with parallel EEG recording. Serotonin gradually increased up to 450% during wakefulness (W) as compared to slow wave sleep (SWS), before decreasing toward stable levels during the next episode of SWS. Dopamine and its metabolite homovanillic acid (HVA) were reduced during W as compared to SWS. Although contradictory with the generally admitted enhancement of DA activity related to vigilance, this may be due to the particular role of DA neurons in the prefrontal cortex. However, DA and HVA showed dramatic changes announcing the transition between SWS and W. During paradoxical sleep (PS), DA and 5-HT showed complex changes, the direction of which depended on whether PS was followed by SWS or W. Biogenic amines of the prefrontal cortex are probably involved in cortical and behavioural activation.

Animals↗

PubMed2000

Conditioned taste aversion in rats for a threonine-deficient diet: demonstration by the taste reactivity test.

Rats avoid a diet that is deficient in one or more essential amino acids (EAAs). This phenomenon is thought to involve the development of a "learned aversion" for the sensory properties or spatial placement associated with the deficient diet. The dietary self-selection technique has been widely used to show this avoidance of the deficient diet. Because avoidance does not necessarily imply taste aversion, we used the Taste Reactivity Test initially created by Grill and Norgren (1978) to analyze the affective reactivity pattern of rats that ingested a threonine-deficient diet. The results showed that there was an increase in the aversive responses when ingesting the threonine-deficient (Thr-Dev) diet, compared to a control diet, without changes in the hedonic responses. The aversive reactions were mainly gaping, and to a lesser extent chin rubbing and head shaking. This asymmetrical shift in the Thr-Dev diet palatability is consistent with a two-dimensional hypothesis of palatability, indicating that the aversive palatability of the deficient diet was increased while the positive palatability did not change. Further evidence indicates that rats do not develop a normal behavioral satiety sequence after ingesting the threonine-deficient diet. These results indicate that a true aversion is formed to the taste of a diet that is deficient in an essential amino acid.

Animals↗

PubMed1999

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.

Animals↗

PubMed1999

Rapid fall in plasma threonine followed by increased intermeal interval in response to first ingestion of a threonine-devoid diet in rats.

In most animals, ingestion of a diet lacking an essential amino acid (EAA) gives rise to anorexia within a few hours. The first signal in this feeding response may be the fall in plasma levels of the limiting EAA. In the present study, we measured plasma amino acid levels and food intake after the first exposure to either a threonine-devoid (THR-DEV) or corrected (COR) diet in 16 rats bearing a chronic jugular catheter for blood sampling. Food intake was reduced 165 min (p<0.05) after presentation of the THR-DEV diet. Analysis of the feeding pattern showed that intake was reduced via a four-fold lengthening of the second inter-meal interval. Plasma threonine levels started to fall between 30 and 60 min after onset of the meal (p<0.05). These results, observed in the same rats, lend further support for an early modification of the plasma amino acid pattern in relation to the decrease in feeding of a diet that is EAA deficient.

Analysis of Variance↗

PubMed1999

Brain insulin response to feeding in the rat is both macronutrient and area specific.

Using microdialysis, we showed recently that hypothalamic immuno-reactive insulin (IRI) levels increased after a meal of chow and decreased in response to a fat meal. In the present study, we have compared extracellular hypothalamic and extrahypothalamic basal IRI levels and investigated the effect of meals composed exclusively of either carbohydrates (85% starch, 15% sucrose) or casein on both plasma and medial hypothalamic (PVN-VMH) insulin. The response of IRI to a carbohydrate meal was also investigated in the cerebellum. Basal hypothalamic IRI was twofold higher in the hypothalamus as compared to the cerebellum (33 +/- 4 and 15 +/- 2 pg/mL, respectively). Hypothalamic IRI increased twofold in response to the carbohydrate meal (72 +/- 15 pg/mL) but remained unchanged during the casein meal. No IRI change was found in the cerebellum after a meal of carbohydrates (16 +/- 2 pg/mL). Insulinemia was increased by both the carbohydrate and the casein meal. However, the protein-induced increase was less pronounced (maximum + 359% compared to 1650% for carbohydrates). The present data show a dual specificity of brain insulin response to feeding; in addition to the macronutrient specific variations, a regional specificity was also observed. Taken together with previous observations, the present data are in favor of an involvement of PVN-VMH insulin in the control of feeding and macronutrient-specific appetites.

Animals↗

PubMed1999

Dopamine turnover in the mediobasal hypothalamus in rat fetuses.

In this study, the dopamine turnover in the mediobasal hypothalamus, the key compartment of the neuroendocrine regulation of reproduction, was evaluated in fetal male and female rats. High-performance liquid chromatography with electrochemical detection was used to measure 3,4-dihydroxyphenylalanine, dopamine and 3,4-dihydroxyphenylacetic acid in the mediobasal hypothalamus of fetuses on the 21st day of intrauterine development and in primary cell culture (cell extracts and culture medium) of the same brain region, explanted at the 17th fetal day and maintained for seven days. The same technique was applied to determine dopamine release from fetal neurons of the mediobasal hypothalamus in response to an excess of K+ in the perifusion system or in culture. L-3,4-Dihydroxyphenylalanine, dopamine and 3,4-dihydroxyphenylacetic acid were detected both ex vivo and in culture. The ratios of the concentrations of L-3,4-dihydroxyphenylalanine/dopamine and 3,4-dihydroxyphenylacetic acid/dopamine were significantly higher in vitro than ex vivo, showing a lower rate of dopamine production and a higher rate of its degradation in the experiments in vitro. Moreover, it has been demonstrated that an excess of K+, i.e. a membrane depolarization, resulted in a highly increased release of dopamine in the perifusion system and in culture. The dopaminergic activity in the developing mediobasal hypothalamus showed sexual dimorphism that was manifested in a greater concentration of 3,4-dihydroxyphenylalanine and dopamine, at least in cell extracts of cultures, as well as in a higher rate of dopamine release, both in the perifusion system and in culture in males compared to females. Thus, dopamine is synthesized and released in response to a membrane depolarization in the mediobasal hypothalamus of rats as early as the end of intrauterine development, suggesting its contribution to the inhibitory control of pituitary prolactin secretion.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Microdialysis and EEG in rats reveal cortical PGE2 changes during sleep and wakefulness.

Prostaglandin (PG) E2 production was assessed in freely moving rats using the technique of microdialysis in the prefrontal cortex associated with parallel cortical EEG recordings. PGE2 concentrations were 40% higher during wakefulness than during slow wave sleep. PGE2 values varied during wakefulness with a maximal increase in the middle of the stage and a drop towards lower values before the occurrence of slow wave sleep. These variations were similar to those observed previously in the rostromedial hypothalamus, where PGE2 concentration was 2.6 times lower than that in the cortex. These data document a positive correlation between cortical EEG activation and PGE2 levels. Taken together with pharmacological data on the awakening effect of centrally administered PGE2, these observations are in favor of an involvement of PGE2 in the generation of wakefulness.

Animals↗

PubMed1998

Spatial cues are relevant for learned preference/aversion shifts due to amino-acid deficiencies.

Rats are able to choose appropriately between two versions of a novel diet, when one is amino-acid devoid and the other corrected. Recognition of the deficiency has been reported to occur within hours and to initiate a strong conditioned aversion. For that purpose the rat can use either oro-sensory cues or another alternative as the conditioned stimulus (CS) with which to associate the unconditioned stimuli (US) of either the adequate diet or the devoid diet. The present investigation was designed to determine whether rats have the ability to use place as a cue in amino-acid preference/aversion. In order to avoid interfering with any other than spatial sensory discrimination between the devoid diet and its corrected version, rats were offered two food cups containing an identical threonine-devoid diet. This was supplemented with an intra-gastric delivery of either threonine or its vehicle, that varied according to the position of the feeder from which the rats had chosen to eat. After three choice sessions, rats chose the food container on the side corresponding to the threonine load. Our results showed that rats use place as a cue for an amino-acid replete nutritional state by learning a conditioned place preference/aversion and that they achieve this type of learning in spite of the long delay elapsing between CS and US.

Amino Acids↗

PubMed1998

Combined effect of obesity and aging on feeding-induced monoamine release in the rostromedial hypothalamus of the Zucker rat.

OBJECTIVE: The obesity of the Zucker rat is associated with numerous metabolic and neurochemical disturbances involving the central transmitters regulating feeding behaviour. Among them, the release of satiety-related monoamines from the median hypothalamus in response to a meal is enhanced in obese, as compared to normal, rats as though larger amounts of these amines were necessary to bring about satiety in obese rats. Besides, the obese Zucker rat has often been described as shorter-living than its lean congener. One of the reasons for the shorter longevity of the obese rat was investigated in this study: it could be an aggravation of its obesity-related central disturbances with age. METHODS: We assessed the response to a meal of the hypothalamic monoamines, dopamine and serotonin, in young (four month old) and old (twelve month old) lean (Fa-Fa) and obese (fa-fa) Zucker rats. The in vivo technique of microdialysis was used to combine behavioural recordings and continuous neurochemical assays. RESULTS: The exacerbation of monoamine release observed in young obese rats in response to a meal was no longer found in old obese rats. Serotonin increase during a meal weakened with aging, especially in obese rats. Dopamine (DA) response to a meal was completely reversed in old obese rats, with a decrease instead of the increase observed in the three other groups. CONCLUSION: The decrease of monoaminergic response to a meal with age is apparently the opposite to the enhanced release related to obesity. However, this does not correspond to an amelioration of the hyperphagia of the obese rats with age, as we could observe in parallel behavioural experiments, but rather to a decrease in neurotransmitter metabolism and thus in neuronal functioning.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Prolactin secretion and its dopamine inhibitory control in rat fetuses.

This study has determined in rats the ontogenetic schedule of the onset of pituitary prolactin (PRL) synthesis and release as well as of the establishment of the dopamine (DA) inhibitory control of PRL secretion. RIA recognized PRL traces in the pituitary at the 18th embryonic day (E18), although a clearly detectable amount of this hormone was first measured at E20, suggesting the onset of PRL synthesis. The PRL level in the pituitary increased significantly by E22, in females to a higher extent than in males. Decapitation of fetuses did not cause any change in the PRL plasma level in males showing no PRL release from the pituitary until term. Conversely, there was a slight but significant fall of plasma PRL in decapitated females, suggesting PRL release from the pituitary. An inhibition of DA receptors on lactotropes of fetuses resulted in an increased level of plasma PRL at E20, but not at E18, while the pituitary content of PRL remained unchanged. The same treatment at E22 caused a significant increase of the PRL concentration in plasma and a concomitant fall in the pituitary that could be prevented by preliminary encephalectomy. These data show that the tuberoinfundibular DA system begins to inhibit PRL release from lactotropes between E20 and E22, completely arresting PRL release from the pituitary in males but not in females.

Animals↗

PubMed1997

Insulin responses to a fat meal in hypothalamic microdialysates and plasma.

In a recent microdialysis study in freely-behaving rats, we observed changes in immunoreactive insulin (IRI) in hypothalamic dialysates after a meal of standard laboratory chow. These changes did not always parallel plasma insulin variations, suggesting a partial independence from peripheral insulin. In the present study, we have attempted to assess the profile of medial hypothalamus (VMPH-PVN) extracellular insulin and peripheral insulin before and after a fat meal (lard). In contrast to the increase we previously observed with chow meals, hypothalamic extracellular IRI decreased during the fat meal and fell to 60% 30 min after the meal. Plasma insulin levels did not change. The intake of the lard meal, provided in unlimited amounts, was much larger in calories than the intake of a chow meal under the same conditions. However, when rats were offered a meal of chow after they had eaten a meal averaging 6.7 g of fat (61 calories), they immediately began eating the chow. Thus, the meal of fat produced no general satiation. On the contrary, the rats consumed a second chow meal only after a delay of approximately 40 min after the first one. The present data, in conjunction with our previous observations with chow fed rats, suggest that the level of extracellular hypothalamic IRI may decrease independently of plasma insulin levels and may, at least partially, account for the observed lack of satiation.

Animals↗