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At least 253 records · Page 14Linked to original sources
PubMed1993

Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic acid excretion in man.

OBJECTIVE: To determine the effect of dietary salt restriction on urinary excretion of serotonin and its principal metabolite 5-hydroxyindoleacetic acid (5-HIAA) in man. DESIGN: We studied 16 healthy male volunteers (age range 20-28 years) who ate a standard diet containing 20 mmol/day NaCl, to which either 220 mmol/day NaCl or placebo was added as a supplement for 1 week each, according to a randomized, single-blind crossover design. METHODS: Urinary excretion of serotonin, 5-HIAA, noradrenaline and vanillylmandelic acid (VMA) were measured during the low- and high-salt periods using reverse-phase high-performance liquid chromatography. RESULTS: During the low-salt diet, 24-h urinary excretion of serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA. Salt restriction also increased noradrenaline excretion by 77% and VMA excretion by 40%. Regression analysis revealed a strong positive relationship between the excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between that of 5-HIAA and of VMA (r = 0.74, P < 0.001). CONCLUSIONS: Salt restriction stimulates the serotonergic system in man. Stimulation of this system, in conjunction with the sympathetic nervous system, may contribute to renal sodium conservation during dietary salt restriction in man.

Adult↗
PubMed1996

5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis.

This study evaluated the relationship between prechemotherapy cortisol and 5-hydroxyindoleacetic acid (5-HIAA) excretion and chemotherapy-induced emesis. The urinary excretion of cortisol and the serotonin metabolite 5-HIAA in the night before chemotherapy administration were measured in 28 and 49 female patients receiving > 300 mg m-2 carboplatin. Vomiting and nausea were documented over a 3 day observation period. Lower basal cortisol excretion was significantly correlated with vomiting with or without nausea occurring within the observation period. 5-HIAA showed only a weak correlation with emesis on days 1-3, but low 5-HIAA excretion was correlated with a higher proportion of patients vomiting on days 2-3 following chemotherapy. Low basal cortisol excretion might be useful as a predictor for chemotherapy-induced emesis and therefore should be evaluated prospectively in future studies.

Adult↗
PubMed1984

Postmortem and regional changes of serotonin, 5-hydroxyindoleacetic acid, and tryptophan in brain.

Using a specific and sensitive high pressure liquid chromatographic technique for the measurement of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan (TRP), we found that there were no changes in 5-HT or 5-HIAA in the rat cortex when left in situ for 6 h at room temperature or 24 h at 4 degrees C. Only a minimal 14% increase in 5-HT was observed after 24 h at 4 degrees C in the striatum of the same animals. Concentrations of TRP, however, were increased significantly in both brain regions by these postmortem delay procedures. A second study revealed that there were significant regional 5-HT and 5-HIAA concentration differences within the cerebral cortex. The frontal cortex was shown to have the highest concentrations of 5-HT and 5-HIAA. Further, within the frontal cortex, 5-HIAA levels varied, showing apparent progressive rostral to caudal increases. 5-HT concentrations, however, remained constant within the frontal cortex. These results are discussed in reference to the conflicting reports of the previous human suicide and postmortem studies.

Animals↗
PubMed1988

5-Hydroxyindoleacetic acid in cerebrospinal fluid reflects serotonergic damage induced by 3,4-methylenedioxymethamphetamine in CNS of non-human primates.

This study examined whether 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) could be used to detect serotonergic damage induced by (+/-)-3,4-methylenedioxymethamphetamine (MDMA) in the central nervous system (CNS) of non-human primates. Monkeys were administered toxic doses of MDMA; two weeks later, the animals were lightly anesthetized with ether and CSF was obtained by means of cervical puncture. Later that same day, the animals were killed for direct determination of CNS serotonin and 5-HIAA concentrations. Monkeys with 73-94% depletions of serotonin and 5-HIAA in brain and 42-45% depletions of serotonin and 5-HIAA in the spinal cord had a 60 +/- 7% reduction of 5-HIAA in CSF, without any change in homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenethyleneglycol (MHPG). These findings indicate that CSF 5-HIAA can be employed to detect central serotonergic damage produced by MDMA in non-human primates, and suggest that CSF 5-HIAA may be useful for detecting MDMA-induced neuronal damage in humans.

3,4-Methylenedioxyamphetamine↗
PubMed1982

A rapid and simple method to determine the specific activities of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan in brain by HPLC with electrochemical detection.

The specific activities of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) have been determined in the brain of rats by HPLC using electrochemical detection. The method allows, from a single sample, the simultaneous measurement of all three compounds and collection of each peak for radioactivity determinations. Five male Wistar rats were injected i.v. with 2.0 mCi/kg of DL-5-hydroxy-[G-3H]tryptophan (2.6 Ci/mmol) and 30 min later the animals were killed by near freezing. Whole brains were removed and homogenized in an acid medium. The content of 5-HTP, 5-HT, and 5-HIAA were determined by HPLC. Each peak of interest was immediately collected after detection in scintillation vials by use of a small dead space detector (TL-9A, Bioanalytical Systems, Inc.). The amounts of radioactivity were determined and specific activities calculated from the results. A second chromatography system (TLC) was used to check the authenticity and purity of compounds separated by the HPLC.

5-Hydroxytryptophan↗
PubMed1982

Rorschach ratings in depressed and suicidal patients with low levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid.

In order to explore the psychodynamics of a previously observed association between a low concentration of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and an increased tendency to suicidal behavior, blind ratings of Rorschach variables were compared between depressed and/or suicidal patients with low (less than 80 nanomoles/l) and normal (greater than 80 nanomoles/l) CSF 5-HIAA. In 14 patient pairs matched for sex, age, body height, and interview-based ratings of severity of depression, the low 5-HIAA subjects had significantly more anxiety and more hostility in the Rorschach ratings. Their anxiety tolerance was lower, and they were significantly less efficient in their handling of conflict. The results support the hypothesis that biochemical variables may be of importance for certain psychodynamic mechanisms suggested to be relevant for psychopathology, including suicidal behavior.

Adult↗
PubMed1990

A modified HPLC technique for simultaneous measurement of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebrospinal fluid, platelet and plasma.

A sensitive, reliable and simplified HPLC assay for simultaneous measurement of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in human cerebrospinal fluid (CSF), platelets and plasma is described. Perchloric acid is used for one step precipitation of proteins and extraction of 5-HT and 5-HIAA. Precision of the assay has been increased by calibration of the instrument using serotonin-free plasma spiked with known amount of standards and N-w-methyl-5-hydroxytryptamine as internal standard. Integration of the peaks and calculations are achieved by a preprogrammed data module using ratio method. As little as 20 pg/ml of serotonin in the deproteinated sample can be detected using this procedure. In a group of surgical patients, plasma 5-HT concentration is (Mean +/- S D) 3.4 +/- 2.7 ng/ml and that of platelet 748.3 +/- 448.3 ng/10(9) platelets. In CSF, 5-HT is found to be 3.3 +/- 3.4 ng/ml and 5-HIAA is 15.1 +/- 7.3 ng/ml. A good correlation (r = 0.648, p less than .0001) is observed between 5-HT and 5-HIAA in CSF.

Adult↗
PubMed1995

Regional 5-hydroxyindoleacetic acid production in humans.

Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain.

Adolescent↗
PubMed1980

Changes in the serotonin and 5-hydroxyindoleacetic acid contents in rat brain after ethanol and disulfiram treatments.

Disulfiram (700 mg/kg, p.o.) significantly increased the brain levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rats. Ethanol (1 g/kg and 2 x 1.5 g/kg, i.p.) did not affect the 5-HT level, but at the higher dose it significantly increased the 5-HIAA level. When disulfiram was given in combination with ethanol, the brain level of 5-HT was significantly higher and, conversely, the 5-HIAA level was significantly lower, as compared to the results with disulfiram alone. These results suggest that the biogenic aldehyde derived from 5-HT may influence 5-HT metabolism and the elimination of 5-HIAA from the brain.

Aldehyde Oxidoreductases↗
PubMed1998

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion during multiple-day high-dose chemotherapy.

Highly emetogenic drugs such as cisplatin induce an increase in the urinary 5-hydroxyindoleacetic acid (5-HIAA) level, the main metabolite of serotonin (5-HT), within the first 24 h following a single infusion, thus providing a possible cause for acute emesis and an explanation for the action of 5-HT3 antagonists. No further excretion peaks have been observed, suggesting that additional or serotonin-independent mechanisms cause delayed emesis. Our aim was to study the mechanisms behind emesis seen during a highly emetogenic chemotherapy regimen given as a continuous infusion over several days. Seven women treated with a 4-day high-dose chemotherapy (HDCT) regimen for breast cancer entered the study. Pooled urine samples were collected prior to and during chemotherapy for determining 5-HIAA excretion. An excretion peak in the urinary 5-HIAA level was observed within the first 24 h with no further peaks thereafter. Thus, the mechanisms behind the emesis experienced during this highly emetogenic multiple-day chemotherapy regimen from days 2-3 onwards would appear to be at least partially serotonin independent and would not be expected to be completely relieved by 5-HT3 antagonists alone.

Adult↗
PubMed1978

Morphine analgesia and the bulbospinal serotonergic system: increase in concentration of 5-hydroxyindoleacetic acid in the rat spinal cord with analgesics.

Administration of an analgesic dose of morphine increased the concentration of the metabolite of 5-hydroxytryptamine (5HT), 5-hydroxyindoleacetic acid (5HIAA), in the spinal cord of rats. The time course of the change in 5HIAA concentration in the dorsal half of the spinal cord corresponded to that of the morphine analgesia, while such was not the case in the ventral half. When the spinal cord was transected at C1, the effect of morphine on 5HIAA concentration disappeared. After transection at the inter-collicular level, this effect remained. The possible relationship between morphine analgesia and descending serotonergic neurons in the spinal cord is discussed.

Analgesics↗
PubMed1984

In vivo voltammetric measurement of extracellular 5-hydroxyindoleacetic acid in the denervated striatum after transplantation of mesencephalic raphe neurons.

In vivo differential pulse voltammetry with carbon fiber electrodes was used to monitor extracellular 5-hydroxyindoleacetic acid (5-HIAA) levels in a serotonergic denervated target area, the striatum, before and after transplantation of mesencephalic raphé nuclei into the lateral ventricle in the rat. The amplitude of the electrochemical signal recorded in the striatum on the transplanted side was found to be comparable to that measured in control striatum whereas the signal measured from the contralateral nontransplanted striatum was negligible. These findings suggest that mesencephalic raphé nuclei transplants establish connections with the host tissue.

Animals↗
PubMed1979

Changes in brain and spinal tryptophan and 5-hydroxyindoleacetic acid levels following acute morphine administration in normal and arthritic rats.

The effects of morphine (10 mg/kg/s.c.) on tryptophan (TRP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were studied in normal and arthritic rats. (1) In normal rats morphine induced a discrete but significant increase of 5-HIAA levels in the forebrain and the spinal cord. (2) By contrast, in rats suffering from experimentally induced arthritis large modifications were apparent. The basal levels of TRP, 5-HT and 5-HIAA were significantly higher than in normal rats. Morphine induced clear increases of 5-HIAA and TRP in the forebrain, the brain stem and the spinal cord, without any modification of 5-HT. The effects were dose-dependent and suppressed by naloxone (1 mg/kg/i.m.). Statistical analysis clearly revealed that arthritic rats were much more sensitive to morphine. The results support the hypothesis of an activation of a 5-HT descending pathway by morphine which parallels the activation of the ascending pathway previously demonstrated by several authors and confirmed here.

Animals↗
PubMedDate not supplied

Dissociation of increased 5-hydroxyindoleacetic acid levels and physical dependence: the effects of naloxone.

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.

Animals↗
PubMed1983

Effect of the antiepileptic di-n-propylacetamide on 5-hydroxytryptamine turnover in the brain and 5-hydroxyindoleacetic acid level in the cerebrospinal fluid.

The effect of antiepileptic drug di-n-propylacetamide (DPM) on 5-hydroxytryptamine (5-HT) turnover in rat brain and 5-hydroxyindoleacetic acid (5-HIAA) in cat cerebrospinal fluid (CSF) was investigated. DPM (200 mg/kg) increased brain 5-HIAA without altering the 5-HT level. DPM augmented the accumulation of 5-HT induced by monoamine oxidase inhibition with pargyline (80 mg/kg) and enhanced the accumulation of 5-HIAA in the brain following blockade of transport of this metabolite by probenecid (200 mg/kg). Prior inhibition of 5-HT synthesis by p-chlorophenylalanine (300 mg/kg) abolished the DPM-induced increase in cerebral 5-HIAA. DPM (100 mg/kg) given daily for 5 days considerably elevated 5-HIAA in the CSF of cat during the treatment period. We conclude that DPM increases the turnover of 5-HT in brain and that this can be observed by monitoring the 5-HIAA content of CSF.

Animals↗
PubMed1993

Stress-induced changes of extracellular 5-hydroxyindoleacetic acid concentrations followed in the nucleus raphe dorsalis and the frontal cortex of the rat.

In the present paper, the effect of different stressors on extracellular 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the frontal cortex and the N. raphe dorsalis (NRD) of the rat were studied. The following stressful procedures were used: Immobilization, 10 min, cold, 20 min, and forced exercise in a rotating wheel, 2h. These procedures were compared with a handling procedure, 10 min. The extracellular 5-HIAA concentration was followed by in vivo voltammetry with carbon multifibre electrodes in the awake animal. Handling had no significant effect on extracellular 5-HIAA concentrations neither in the frontal cortex nor the NRD, whereas immobilization and cold evoked significant increases in both brain areas. During and after forced exercise a significant increase was measurable only in the frontal cortex, while extracellular 5-HIAA concentrations were unchanged in the NRD. Since it is very likely that the modulation of the activity of the central serotoninergic system under stressful conditions is closely connected with changes in behaviour and temperature regulation, we compared our findings on extracellular 5-HIAA levels during stress with the effect of the 5-HT1A agonist (+)-8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT), a substance known to reduce body temperature. The i.p. injection of a low dose decrease significantly both, the extracellular 5-HIAA concentration in the NRD and body temperature. Our results suggest that the serotoninergic activation in the frontal cortex may prove to be a general response to stress which could function perhaps as a part of the central coping mechanism, whereas serotonin (5-HT) in the NRD may modulate specific regulatory responses such as body temperature.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

On the concentration of 5-hydroxyindoleacetic acid in schizophrenia: a meta-analysis.

A meta-analysis was performed on the results of a number of investigations of concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid, serum, or urine of acute and chronic schizophrenic patients. Only those studies were chosen in which some degree of age and gender matching were achieved and in which the comparison subjects were healthy normal volunteers. Fisher's procedure and a weighted Liptak method revealed no significant differences between normal subjects and schizophrenic patients, indicating that disturbances of serotonergic turnover do not, in general or essentially, contribute to the etiology of schizophrenia.

Acute Disease↗