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D Laude

Publications and source records attributed to D Laude.

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Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat.

An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasma free Trp was decreased after 2 h of running. Liver Trp content rose only after 3 h of running, while liver unesterified fatty acid (UFA) concentrations remained unmodified. A comparison between food deprivation and running (both of which promote lipolysis) was performed. Running for 2 h affected to the same extent plasma Trp disposition when compared with 24 h food deprivation. Nevertheless, the ratio of brain Trp to plasma free Trp was decreased in the food-deprived rats, when compared to the runners. Nicotinic acid, which inhibits fat catabolism, completely abolished the plasma UFA increase induced by 1 h of running. The drug did not affect plasma free Trp, brain Trp, 5-HT or 5-HIAA but enhanced plasma total Trp level. Naloxone, an opiate antagonist, which decreased running-induced lipolysis, did not alter plasma Trp disposition. Desipramine, an antidepressant compound, affected only peripheral Trp concentrations of the runners. Plasma free and total Trp concentrations were increased in desipramine-treated runners, compared with saline-treated runners. In addition, desipramine increased the ratio of brain Trp to plasma free Trp of the runners. Brain 5-HT and 5-HIAA were increased in both desipramine-treated controls and runners. 9 The results suggest that running, which like food deprivatiQn accelerates lipolysis, increases brain Trp content and then 5-HT turnover. Comparison of these two physiological situations suggests that effectiveness of brain Trp entry is much more altered by fasting.

Animals↗

Pizotifen increases 5-HIAA urinary excretion in male healthy volunteers.

A single dose of 0.5 mg pizotifen or a placebo was administered to 10 healthy male volunteers in a double blind cross-over trial. 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in hourly urine samples were determined by liquid chromatography with amperometric detection. The 5-HIAA levels were strongly correlated with the HVA levels in control samples (r = 0.95, p less than 0.001). Pizotifen produced a significant increase in the urinary 5-HIAA/HVA ratio over the 3 hours following absorption of the drug (+0.21, +0.18, +0.19, p less than 0.05). The increase demonstrates an interaction between pizotifen and 5-HT metabolism, which may be involved in its antimigraine effect.

Adult↗

Kinetics of drug-induced changes in dopamine and serotonin metabolite concentrations in the CSF of the rat.

Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Every 15 min, CSF dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined by direct injection of CSF into a liquid chromatographic system coupled with electrochemical detection. Mean CSF concentrations of DOPAC, HVA, and 5-HIAA were 1.29 microM, 0.88 microM, and 2.00 microM, respectively. In order to determine the turnover rates of dopamine (DA) and serotonin, experiments using monoamine oxidase (MAO) inhibition were performed. Tranylcypromine (20 mg/kg i.p.) induced a sharp exponential decrease of CSF DOPAC, HVA, and 5-HIAA, with respective half-lives of 15.60 min, 16.91 min, and 77.23 min. Their respective turnover rates were 3.74, 2.22, and 1.18 nmol X ml-1 X h-1. m-Hydroxybenzylhydrazine (NSD-1015, 100 mg/kg i.p.) and monofluoromethyl-DOPA (100 mg/kg i.p.), two decarboxylase inhibitors, induced a slow exponential decrease of all three CSF metabolites. alpha-Methyl-p-tyrosine (250 mg/kg i.p.) also induced a slow exponential decrease of DOPAC and HVA. These decreases of CSF DOPAC and HVA induced by DA synthesis inhibitors may reflect the turnover of DA in vivo. Haloperidol (0.5 mg/kg i.p.) considerably enhanced CSF DOPAC and HVA without affecting 5-HIAA, confirming that dopaminergic receptors modulate DA neurotransmission in vivo. Haloperidol administered 1.5 h after NSD-1015 did not increase DOPAC and HVA, in contrast to reserpine (5 mg/kg i.p.) injected under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Brain amine metabolism is reflected in cerebral ventricular CSF.

The choroid plexuses are suspended within the ventricles and account for approximately 75% of CSF production. The sodium-potassium ATPase operates within the choroidal epithelial cells and moves sodium ions towards the ventricular surface and potassium ions in the direction of the stroma. Water flows into CSF along osmotic gradient produced by sodium pump. The existence of extracellular channels by which brain metabolites could passively diffuse into the ventriculosubarachnoid space suggests an excretory role for CSF. Removal of solutes from the CSF could occur across the choroidal epithelium or arachnoid membrane into the blood. Systematically administered monoamine metabolites do not cross the blood-brain or the blood-CSF barrier. The regional concentrations of amine metabolites in the CSF is in part a reflection of the concentration of catecholamines and indoleamines in the immediately adjacent neuronal parenchyma. In order to illustrate the validity of monoamine metabolite determinations in cerebral ventricular CSF we developed a device which allowed for a continuous third ventricular CSF withdrawal in freely moving (or anesthetized) rats at a constant flow of 1 microliter/min. The elevation of biogenic amine metabolites in CSF by probenecid or their decline by monoamine oxidase inhibition was used to assess the rate of turnover of amines. Pharmacological manipulations (yohimbine, haloperidol, ouabain) resulted in mono-amine metabolite fluctuations in CSF similar to those previously described in brain tissue. Insulin administration caused an abrupt decrease in CSF glucose and elevated dopamine and serotonin metabolites in rats which had no access to food. These studies demonstrate the adaptation of in vivo analysis of CSF in rats but also exemplify the usefulness of monoamine metabolite determination in the CSF as indicators of brain function.

Amines↗

Determination of alphamethyldopa, dihydroxyphenylacetic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid of the rat: kinetic study.

Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter min-1 from the third ventricle of rats and directly analyzed by liquid chromatography coupled with electrochemical detection. The effect of alphamethyldopa (alpha MD) on CSF alpha MD, dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolacetic acid (5-HIAA) concentrations was studied for 5 h. alpha MD ethyl ester administration resulted in higher alpha MD levels in CSF as compared with alpha MD administration, suggesting a higher bioavailability of the ethyl ester vs the free acid. A specific inhibition of dopamine metabolism was reflected by a reduction in DOPAC levels while 5-HIAA concentrations were unchanged.

3,4-Dihydroxyphenylacetic Acid↗

Central administration of yohimbine increases free 3-methoxy-4-hydroxyphenylglycol in the cerebrospinal fluid of the rat.

The effect of the alpha2-antagonist, yohimbine, on cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindolactic acid (5-HIAA) concentrations was studied in vivo. Cerebrospinal fluid was removed at a constant flow rate of 1 microliters/min from the third ventricle of rats and directly analysed by liquid chromatography coupled with electrochemical detection. An intracerebroventricular injection of yohimbine (100 nmol) dramatically increased MHPG levels. These results suggest a functional stimulation of alpha-2 adrenoceptors modulating noradrenergic neurotransmission in vivo.

3,4-Dihydroxyphenylacetic Acid↗

Anger expression and cardiovascular reactivity to mental stress: a spectral analysis approach.

The cardiovascular reactivation to a recently described videogame task i.e. a maze test was evaluated in the time and frequency-domain using finger blood pressure (BP) measurement in 25 subjects on no medication, including 6 subjects with mild hypertension. Prior to BP measures subjects completed the items of the State-Trait Anger Expression Inventory questionnaire corresponding to the trait anger and anger expression scales. The BP recording session was divided into resting, test and recovery periods. A detrending procedure was applied to each recording prior to the fast Fourier transform. Systolic BP (SBP) and heart rate (HR) were increased during the test. The mid-frequency (MF, 0.1 Hz) components of SBP and HR variability were also elevated during the stressful period. In resting conditions SBP levels of subjects with low trait anger was lower than in subjects with high trait anger (128 +/- 4 mmHg, n = 14 versus 148 +/- 4 mmHg, n = 11, P < 0.01, Student t test). Nevertheless the average SBP increase due to the stress was of similar magnitude in these two subgroups (14 mmHg). A significant negative relationship was observed between anger-out expression score and the MF SBP variation (r = 0.46, P < 0.05). A significant negative relation was found between anger-in mode of expression and the HR peak during the test (r = 0.43, P < 0.05). In conclusion, our data suggest that individuals who are often in anger-provoking situations (high trait anger) should have heightened BP. Two different patterns of cardiovascular responses (SBP variability and HR levels) were observed for the outward and inward mode of expression of anger. This may reflect a different psychological control of HR levels and BP variability.

Adult↗

[The effects of cerebral ischemia on the level of metabolites of dopamine and serotonin in the rat cerebrospinal fluid].

Hemispheric ischemia was induced in normothermic, artificially ventilated and anesthetized rats, by electrocauterization of the vertebral arteries and a transient occlusion of the common carotid arteries for 10 minutes. Cerebrospinal fluid (CSF) was continuously pumped out of the third cerebral ventricle for potassium, dopamine and serotonin metabolite determinations. Levels were stable until ischemia, which interrupted the CSF production. During early recirculation a marked increase in dopamine metabolites occurred. The metabolite of serotonin increased slightly with a delay. Potassium in CSF was transitorily increased following ischemia. Reserpine pretreatment prevented most of the changes such as the early increase in dopamine metabolites. A delayed increase of these metabolites was still observed. This model of short ischemia altered the neurological functioning and survival time of the animals especially 15 minutes after removal of bilateral carotid occlusion, as compared to the later periods of observation. This model is therefore applicable to the study of cerebral alterations secondary to ischemia in vivo. The presently observed alterations of metabolite levels could reflect an increased neuronal release of parents monoamines that could participate to the neurological deficit.

3,4-Dihydroxyphenylacetic Acid↗

Species differences in mammalian renal function: 5-HIAA, a reported marker of tubular secretion in humans, is handled exclusively by filtration in the rat.

Renal clearance of endogenous 5-HIAA has been shown to be similar to that of PAH in humans. The present study compared 5-HIAA and PAH clearances in rats. It showed that the clearance of 5-HIAA in rats was identical to that of inulin and creatinine. This suggests that in this species, 5-HIAA is only filtered and not secreted by the tubules in contrast to what is observed in humans.

Animals↗