Biomedical subjects

D Laude

Publications and source records attributed to D Laude.

At least 73 records · Page 4Linked to original sources

PubMed1989

Peripheral and central consequences of immobilization stress in genetically obese Zucker rats.

Peripheral and central effects of acute and chronic immobilization stress were measured in lean and obese Zucker female rats. Thus hypothalamic serotonergic metabolism was analyzed by measuring the concentrations of serotonin (5-hydroxytryptamine, 5-HT), tryptophan (TRP; the precursor of 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA; 5-HT metabolite). In addition, plasma total TRP, free fatty acid (FFA), insulin, and corticosterone concentrations were measured. Analysis of stress-induced changes in food consumption were also included. A single 2-h restraint stress was found to increase TRP availability in the hypothalamus of both rats; this promoted an increase in 5-HIAA in the lean rats and increases in 5-HT and 5-HIAA in the obese (fa/fa) rats. These modifications were associated with marked decreases in plasma total TRP and insulinemia in the lean and obese rats. Whereas stress triggered similar hypercorticosteronemia and hyperglycemia, FFA was increased in the lean rats only. Consecutive hypophagia was noted in all the rats. Twenty-four hours after the last of the four 2-h stress sessions, hypothalamic 5-HIAA was increased in the obese rats and plasma TRP and FFA levels decreased in both rats. Although both groups of rats were normoglycemic, stress-induced hyperinsulinemia was evidenced in the lean rats, thus suggesting that chronic stress promotes insulin resistance. These metabolic variations were associated with normal food consumption and increased body weight gains in the lean and obese Zucker rats.

Animals↗

PubMed1989

Duration of streptozotocin diabetes influences the response of hypothalamic serotonin metabolism to immobilization stress.

Neurochemical and metabolic effects of acute (immobilization for 2 h) and chronic (immobilization for 2 h/day for 4 consecutive days) stress were investigated in diabetic female rats either pretreated 1 week or 5 weeks earlier with streptozotocin (STZ). Hypothalamic serotonin (5-hydroxytryptamine, 5-HT) metabolism was estimated by measuring the respective levels of 5-HT precursor, the amino acid tryptophan (TRP), 5-HT and the 5-HT metabolite, namely 5-hydroxyindoleacetic acid (5-HIAA). To assess the respective metabolic effects of stress and diabetes, plasma total TRP, insulin, glucose and corticosterone levels were measured. Short- and long-term STZ treatment triggered marked decreases in plasma total TRP and hypothalamus TRP levels but the diabetogenic agent diminished 5-HT metabolism in the 1-week ST-treated rats only. Acute stress promoted a marked decrease in plasma total TRP in the vehicle-treated rats and in the 1-week-diabetic rats, which was associated with significant increases in hypothalamic TRP and 5-HIAA levels. In the 5-week-diabetic rats, a single restraint affected neither peripheral and central TRP levels nor hypothalamus 5-HT metabolism. Acute stress triggered hypercorticosteronemia in all groups of rats but it promoted hyperglycemia and hypoinsulinemia in the vehicle-injected rats only. Twenty-four hours after the fourth immobilization, plasma total TRP was reduced in the vehicle-injected rats only with no effect on hypothalamic levels of TRP. On the other hand, chronic restraint was found to reduce exclusively hypothalamus 5-HT and 5-HIAA levels in the 5-week-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

[5-HIAA: perspectives in nephrology].

5-Hydroxyindoleacetic acid (5-HIAA) is the chief end-product of serotonin metabolism. The gastrointestinal tract is the main source of urinary 5-HIAA. The rest originates from the degradation of brain or platelet serotonin stores. Main abnormalities in 5-HIAA excretion have been observed in carcinoid tumors (elevation) or hyperphenylalaninemia (diminution) as well as in migraine. Estimation of renal blood flow is a new application of 5-HIAA measurements. This stems from the elimination process of this weak organic acid which combines glomerular filtration and proximal tubular secretion. Thus 5-HIAA is extracted by the kidney in high amounts as indicated by a high renal extraction ratio. The renal clearance of 5-HIAA seems a good estimation of renal blood flow. Therefore fluctuations of this endogenous compound could be used to quantify the effects of physiological manipulations or drugs on renal blood flow.

Animals↗

PubMed1989

[Effect of transcranial electrical stimulation on sleep in rats].

Transcranial electrical stimulation with high frequency intermittent current (Limoge's current) was delivered to normal rats and to PCPA-treated rats with impaired sleep. Electrocorticogram was continuously recorded for quantifying the stage of the sleep-waking cycle. The current did not affect the sleep pattern of normal rats whereas the number of paradoxical sleep episodes increased in insomniac animals. The increased duration of paradoxical sleep in PCPA-treated rats favored the recovery of sleep in this group. The stimulation increased the brain serotonin turnover, which could possibly contribute to its hypnogenic action.

Animals↗

PubMed1988

Feeding responses to a high dose of 8-OH-DPAT in young and adult rats: influence of food texture.

The present study was undertaken to investigate the hyperphagic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in young and adult rats fed either a powder diet or pellets. In the young rats, 8-OH-DPAT (500 micrograms/kg s.c.) increased the consumption of pellets--but not powder--during the 2 h following drug administration. On the other hand, 8-OH-DPAT did not promote hyperphagia in adult rats presented with either pellets or a powdered diet. The influence of the 5-HT1A agonist on midbrain serotonin (5-hydroxytryptamine, 5-HT) turnover was examined. Administration of 8-OH-DPAT (500 micrograms/kg s.c.) induced similar decreases in 5-HT turnover, as reflected by the ratio of 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT, in young and adult rats 1 h after administration. Nevertheless, some metabolic responses to 8-OH-DPAT were found to be influenced by age. Young and adult rats were injected with a low dose of 8-OH-DPAT (50 micrograms/kg s.c.) to specifically test the presynaptic regulation of 5-HT turnover. Again, midbrain 5-HIAA to 5-HT ratios were decreased to the same extent in both young and adult rats. The results suggest that (i) gnawing may be an important parameter in the food consumption that is triggered by a high dose of 8-OH-DPAT, (ii) analysis of the presynaptic effects of 8-OH-DPAT on 5-HT turnover cannot solely explain the influence of the agonist on feeding behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1988

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Aging↗

PubMed1988

Alpha-adrenoceptors in Dahl hypertensive and normotensive rats: effect of sodium.

Sodium ions play an important role in vitro and in vivo in the regulation of alpha 2-adrenoceptors. The in vitro effect of sodium on cerebral and renal alpha-adrenoceptors was investigated in Dahl salt-sensitive and salt-resistant rats. Cerebral alpha 2-adrenoceptor densities were higher in Dahl salt-resistant rats. In contrast, the renal alpha 2-adrenoceptor density was higher in Dahl salt-sensitive than in Dahl salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between the two types of rat. Noradrenaline contents in the cerebral and renal cortex were also similar in these two rat substrains. An influx of sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in Dahl salt-sensitive but not in Dahl salt-resistant rats. Under these conditions alpha 1-adrenoceptor densities remained unchanged. The absence of sodium regulation in Dahl salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the alpha 2-adrenoceptor system. We conclude from the present study that there are marked differences in density and in the role of sodium regulation of cerebral and renal alpha 2-adrenoceptors from salt-sensitive and salt-resistant Dahl rats. These differences may play a primary role in the resistance or in the sensitivity of salt-induced hypertension.

Animals↗

PubMed1988

Comparative pharmacokinetics of D- and L-alphamethyldopa in plasma, aqueous humor, and cerebrospinal fluid in rabbits.

The 2 stereoisomers of alphamethyldopa (alpha MD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300-min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose-dependent entry of alpha MD was observed in AH. A stereospecific active transport of alpha MD was evidenced in the AH since the concentration of the L-isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the L-stereoisomer was still observed in CSF. These alpha MD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.

Animals↗

PubMed1987

Amphetamine and alpha-methyl-p-tyrosine affect the exercise-induced imbalance between the availability of tryptophan and synthesis of serotonin in the brain of the rat.

This study was performed to investigate the effects of exercise on the synthesis of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain of the trained rat. The consequences on the relationships between these two systems were also examined. The sum of the levels of free 3,4-dihydroxyphenyl acetic acid (DOPAC) plus homovanillic acid (HVA) was increased by running and remained elevated throughout the first hour of recovery. Regional studies indicated that the levels of DA were increased in the midbrain, hypothalamus and hippocampus. In these areas, DOPAC showed little variation whereas HVA was largely increased. Administration of pargyline confirmed this increase in the metabolism of DA in hypothalamus and midbrain during running. Food deprivation and administration of tryptophan clearly revealed that running, despite increasing levels of tryptophan and 5-hydroxyindoleacetic acid in brain, reduced the central control of synthesis of 5-HT by tryptophan, probably by inhibiting tryptophan hydroxylase. To examine if such an alteration was caused by the running-induced activation of metabolism of DA in brain, compounds known to affect the activity of DA were used. Administration of amphetamine potentiated the relative inhibition of synthesis of 5-HT induced by running, while alpha-methyl-p-tyrosine prevented this effect of exercise. Haloperidol did not produce any significant change. It is concluded that the control of the synthesis of 5-HT in brain by the availability of tryptophan is altered during exercise and that the increased central catecholaminergic activity participates in such an alteration.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Platelet cytosolic free Ca2+ concentration and serotonin (5-HT) content in essential hypertension.

Cytosolic free [Ca2+] and serotonin (5-HT) content were measured in platelets from 22 untreated hypertensive patients and 16 normotensive subjects. In hypertensive patients, cytosolic free [Ca2+] was significantly higher (239 +/- 13 nmol/l versus 186 +/- 7 nmol/l, n = 22 and 16, P less than 0.01) and 5-HT content was significantly lower than those measured in cells from control subjects (3.22 +/- 0.26 versus 4.99 +/- 0.38 X 10(-7) mol/10(11) cells, n = 22 and 16, P less than 0.001). These two parameters were closely correlated (r = -0.565, n = 38, P less than 0.001). These two concomitant changes in platelet characteristics might result from a common cause, such as cell membrane alterations. As ritanserine, a specific 5-HT2 receptor antagonist, did not modify the cytosolic free [Ca2+], a higher stimulation of 5-HT2 receptors is not likely to be responsible for the enhanced free Ca2+ levels.

Adult↗

PubMed1986

Changes in central alpha-adrenoceptors and noradrenaline content after high sodium intake in Sabra salt-sensitive and salt-resistant rats.

Several studies have suggested a correlation between sodium accumulation and the development of hypertension. However, the mechanisms whereby sodium is able to increase blood pressure remain unclear. In the present study, alpha-adrenoceptors and noradrenaline contents have been studied in the cerebral cortex, hypothalamus and medulla oblongata in the Sabra rat strain in order to define their role in the resistance or sensitivity to sodium-induced hypertension. Alpha-Adrenoceptors were defined using the selective ligands 3H-prazosin and 3H-rauwolscine for alpha 1- and alpha 2-adrenoceptors, respectively. Under normal sodium diet, alpha 2-adrenoceptor density was higher in cerebral cortex and lower in hypothalamus and medulla oblongata of SBN (salt-resistant) compared to SBH (salt-sensitive) rats. Five weeks of high sodium intake induced a decrease in alpha 2-adrenoceptor density in cerebral cortex and an increase in hypothalamus only in SBN rats. These changes abolished the differences between SBH and SBN rats observed with a normal sodium diet. No changes in density and affinity of alpha 2-adrenoceptors were observed in medulla oblongata of SBN and SBH rats. Density and affinity of alpha 1-adrenoceptors were similar in SBN and SBH rats in all the tissues studied and they were unaffected by the high sodium diet. Noradrenaline contents in cerebral cortex, hypothalamus and medulla oblongata were also similar in the two rat substrains under normal sodium diet, but high sodium intake induced a decrease cerebrocortical noradrenaline content only in SBN rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Peripheral and central short-term effects of fusaric acid, a DBH inhibitor, on tryptophan and serotonin metabolism in the rat.

Fusaric acid (FA) administration to the rats promoted one hour later a large decrease in plasma total tryptophan (TRP), without affecting either plasma free TRP or lipolysis, as measured by plasma non esterified fatty acid concentration. The previous change was associated with hypoinsulinemia, hyperglycemia and increased plasma corticosterone level. Regression analysis revealed a significant correlation between brain TRP and the percentage of plasma TRP which was free (i.e. unbound to albumin), both increased by FA injection. The increase in brain TRP promoted an increased brain serotonin synthesis, as measured by the enhanced brain and CSF 5-HIAA levels. Valine pretreatment, which blocks TRP entry into the brain, completely prevented FA-induced brain TRP and brain 5-HIAA increases. These results suggest that the increased brain serotonergic turnover following FA treatment was due to a peripheral action of the drug upon TRP disposition. The latter effect may be caused (i) by in vivo peripheral alterations in catecholaminergic metabolism and (ii) by FA chemical structure since in vitro experiments revealed that FA was able to displace TRP binding to albumin, thus increasing the plasma free TRP pool.

Animals↗

PubMed1986

Urinary 5-HIAA in migraine: evidence of lowered excretion in young adult females.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in 44 young adult migraine patients (35 women, 9 men) between attacks and in 33 healthy controls (23 women, 10 men). HVA excretion was equivalent in all groups. 5-HIAA was unaltered in men but was significantly decreased in female migraine patients when compared with their sex-matched controls (-31%, p less than 0.01). No relationship was found between 5-HIAA excretion and the various characteristics of migraine, such as the time that had elapsed since the last attack and the presence or absence of oral contraception. The relatively marked decrease in 5-HIAA excretion in female migraine patients can hardly be accounted for by a reduction in either neuronal or platelet serotonin metabolism alone. A reduction in the intestinal contribution to urinary 5-HIAA might be the crucial factor.

Adult↗

PubMed1986

Motor activity increases tryptophan, 5-hydroxyindoleacetic acid, and homovanillic acid in ventricular cerebrospinal fluid of the conscious rat.

An investigation was made into the effects of running (1 h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.

Animals↗

PubMed1985

Fusaric acid-induced elevation of homovanillic acid in the CSF as an index of brain noradrenaline synthesis.

The effect of the dopamine-beta-hydroxylase inhibitor, fusaric acid (FA), on cerebrospinal fluid (CSF) homovanillic acid (HVA) was studied in pentobarbitone-anesthetized rats. Idazoxan, a selective alpha 2-antagonist, accentuated the FA-induced HVA elevation in CSF while alpha-methyldopa pretreatment prevented this effect of FA on the HVA level in CSF. These results could indicate that the rate of dopamine synthesis in noradrenaline neurons could be the main determinant of the FA-induced HVA elevation.

Animals↗

PubMed1985

Measurement of 5-HIAA levels in ventricular CSF (by LCEC) and in striatum (by in vivo voltammetry) during pharmacological modifications of serotonin metabolism in the rat.

The relationship between the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the CSF and in the striatum has been evaluated in the rat by measuring the levels of this metabolite in ventricular CSF (by liquid chromatography coupled with electrochemical detection) and in the striatal extracellular fluid (by in vivo voltammetry) after administration of inhibitors of serotonin synthesis or degradation. Pargyline, NSD 1015 and alpha-propyldopacetamide all caused an exponential decline of 5-HIAA in both CSF and striatum. For a given drug, the rate constants for 5-HIAA disappearance were identical in the CSF and in the striatal extracellular fluid. These results confirm the view that CSF 5-HIAA may serve as a good index of brain serotonin turnover.

Amides↗

PubMed1985

Effects of saltwater adaptation on serotonin metabolite concentrations in the cerebrospinal fluid of rainbow trout (Salmo gairdneri).

A new procedure was applied to rainbow trout for collecting cerebrospinal fluid (CSF). CSF was withdrawn continuously from the third ventricle at a flow rate of 0.7 microliter/min for up to 6 hr. The 5-HIAA concentrations in trout CSF are temperature-dependent and decrease exponentially after pargyline injection. The computed half-life of 5-HIAA production in CSF is 78 min at 15 degrees C. 5-HIAA concentrations in CSF are considered to reflect serotonin (5-HT) metabolism. The 5-HIAA content in the CSF of trout held in freshwater for several weeks is significantly higher than in trout held in either 1.6 or 3.0% saltwater while sodium content only exhibits a very slight change in the CSF of trout held in 3.0% saltwater. It is hypothesized that 5-HT could participate in the neurally-mediated adaptation to various osmotic conditions.

Animals↗

PubMed1985

Study of dopamine turnover by monitoring the decline of dopamine metabolites in rat CSF after alpha-methyl-p-tyrosine.

CSF was continuously withdrawn from the third ventricle of anesthetized rats. CSF 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid concentrations were determined every 15 min by liquid chromatography coupled with electrochemical detection. Acute tyrosine hydroxylase inhibition [with alpha-methyl-p-tyrosine (alpha-MPT)] induced an exponential decline in levels of DOPAC and HVA in CSF. The decline in DOPAC and HVA concentrations was identical in CSF and forebrain but was much slower in the striatum, suggesting that CSF metabolites of 3,4-dihydroxyphenylethylamine (dopamine) reflect whole forebrain metabolites. The decay in CSF DOPAC and HVA levels after dopamine synthesis inhibition was also used as an in vivo index of forebrain dopamine turnover after various pharmacological treatments. Haloperidol pretreatment accelerated this decay, confirming the increase in brain dopamine turnover induced by neuroleptics. After reserpine pretreatment (15 h before), alpha-MPT produced a very sharp decay in levels of DOPAC and HVA. This result indicates that the residual dopamine that cannot be stored after reserpine treatment is very rapidly renewed and metabolized. Nomifensine strongly diminished the slope of DOPAC and HVA level decreases after alpha-MPT, a result which can be explained either by a slower dopamine turnover or by the involvement of storage dopamine pools. These results exemplify the use of monitoring the decay of dopamine metabolites after alpha-MPT administration in the study of the pharmacological action of drugs on the central nervous system of the rat.

3,4-Dihydroxyphenylacetic Acid↗