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PubMed1990

Serotonin and 5-hydroxyindoleacetic acid are increased in the sigmoid colon in severe idiopathic constipation.

The distribution of serotonin and dopamine beta-hydroxylase was examined in sigmoid colon specimens from patients with severe idiopathic constipation and control patients with carcinoma of the rectum or colon. Specimens were divided into three regions: (a) the mucosa; (b) the myenteric and submucosal plexuses with the longitudinal and circular smooth muscles; and (c) the circular smooth muscle, for biochemical analysis of serotonin and 5-hydroxyindoleacetic acid (total indoles) and noradrenaline. In both groups of patients, serotonin- and dopamine beta-hydroxylase-like immunoreactivity was localized in nerves in the myenteric and submucosal plexuses, and a sparse innervation was observed in the circular muscle. In addition, intense serotonin-like fluorescence was present in a large number of enterochromaffin cells in the mucosa. Total indole levels were significantly increased in the mucosa (p less than 0.02) and circular muscle (p less than 0.05) of the constipated patients. In contrast, no changes in noradrenaline levels were observed in any of the regions studied. Altered levels of total indoles may thus contribute to severe idiopathic constipation. Analysis of biopsy specimens could be a useful tool in clinical diagnosis and future investigations of diseases of the gut.

Adult↗
PubMed1975

The effect of high cervical cordotomy on portal vein plasma serotonin and 5-hydroxyindoleacetic acid levels in dogs with and without superior mesenteric artery occlusion.

In ten dogs undergoing high cervical cardotomy, there was a statistically significant fall in plasma serotonin (5-HT) levels in portal vein blood; no further change in plasma 5-HT occurred after superior mesenteric artery (SMA) occlusion, which is an effective stimulus for 5-HT release. In five dogs undergoing high cervical corotomy with no SMA occlusion, there was a comparable fall in portal vein plasma 5-HT levels. The 5-hydroxyindoleacetic acid (5-HIAA) values in portal vein blood in the two groups of dogs above fell to comparable levels. These findings indicate (1) that maintenance of the normal plasma 5-HT level in portal vein blood in this experimental model is dependent on the integrity of the spinal cord and (2) that SMA occlusion in animals with a high cervical cordotomy does not result in further changes in the plasma 5-HT level in portal vein blood.

Animals↗
PubMed1987

Determination of serotonin and 5-hydroxyindoleacetic acid in guinea pig and human prostate using HPLC.

The finding of significant numbers of endocrine-paracrine (EP) cells in the prostate glands of guinea pigs and man suggests that these cells may be important in the regulation or modulation of prostatic function. Serotonin is a biogenic amine common to most prostatic EP cells. In order to extend current knowledge relating to these cells, an assay was developed using high-performance liquid chromatography to quantitate serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in guinea pig and human prostatic tissue extracts. Levels of serotonin and 5-HIAA in the guinea pig whole-gland preparation were 105.4 +/- 70.6 ng/g and 48.4 +/- 95.7 ng/g, respectively. Normal human prostatic tissue contained 1423.9 +/- 750.8 ng/g serotonin and 66.7 +/- 92.8 ng/g 5-HIAA. Recoveries ranged between 60 and 100%. The detection limits were 24 pg/injection for serotonin and 12 pg/injection for 5-HIAA. This assay provides an expeditious, specific and highly sensitive method for the simultaneous determination of monoamines in guinea pig and human prostatic tissue.

Aged↗
PubMed1992

Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy.

Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA.

Adult↗
PubMed1994

Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism.

BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Adult↗
PubMed1997

High serotonin and 5-hydroxyindoleacetic acid levels in limbic brain regions in a rat model of depression: normalization by chronic antidepressant treatment.

Although alterations in serotonin levels and neurotransmission are associated with depressive disorders and effective antidepressant therapy, the exact cause of these disorders and the mode of action of antidepressant drugs are poorly understood. In a genetic rat model of depression [Flinders sensitive line (FSL) rats], deviations from normal serotonin (5-HT) levels and metabolism in specific brain regions were determined. The levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in tissue punches of various brain regions were quantitated simultaneously with an HPLC apparatus coupled to an electrochemical detector. In the nucleus accumbens, prefrontal cortex, hippocampus, and hypothalamus of FSL rats, the levels of 5-HT and 5-HIAA were three- to eightfold higher than in control Sprague-Dawley rats. Significant differences in the levels of 5-HT and 5-HIAA in the striatum and raphe nucleus of the "depressed" and normal rats were not observed. After chronic treatment with the antidepressant desipramine (5 mg/kg/day for 18 days), the immobility score in a swim test, as a measure of a behavioral deficit, and 5-HT levels of the FSL rats became normalized, but these parameters in the control rats did not change. The [5-HIAA]/[5-HT] ratio was lower in the nucleus accumbens and hypothalamus of the FSL than in the control rats, and increased after desipramine treatment only in the nucleus accumbens of the FSL rats. These results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased 5-HT levels in specific limbic sites and suggest the FSL rats as a novel model for clarification of the molecular mechanism of clinically used antidepressant drugs.

Animals↗
PubMed1988

Changes in arterial blood pressure lead to baroreceptor-mediated changes in norepinephrine and 5-hydroxyindoleacetic acid in rat nucleus tractus solitarius.

Catecholamine and indoleamine metabolism in nucleus tractus solitarius were studied during drug-induced hypertension and hypotension. Urethane-anesthetized normotensive male Sprague-Dawley rats implanted with a 250-mu carbon paste in vivo electrochemical electrode were infused with phenylephrine to raise blood pressure 50 mm Hg. Other animals were given nitroprusside to lower pressure 20 mm Hg. Phenylephrine-induced hypertension was associated with a 30% reduction in the electrochemical peak corresponding to norepinephrine. The electrochemical peak which was identified as 5-hydroxyindoleacetic acid (5-HIAA) was increased 25% with the onset of hypertension and remain elevated after the phenylephrine infusion was stopped. Nitroprusside-induced hypotension resulted in a 20% reduction in the norepinephrine peak during the infusion followed by an additional 10% reduction after the infusion. 5-HIAA concentration did not change during the hypotensive phase but showed a 40% increase after the nitroprusside was stopped as blood pressure rebounded to levels higher than the control period. Direct tissue assays of norepinephrine and 5-HIAA confirmed the electrochemical findings. These experiments were repeated in rats which had undergone sinoaortic denervation. The electrochemical changes in norepinephrine and 5-HIAA associated with hypertension and hypotension were attenuated in these animals indicating that the brain neurotransmitter changes were a consequence of baroreceptor input to the brain. We conclude that 5-HIAA in nucleus tractus solitarius appears to be a marker for elevated blood pressure, whereas norepinephrine falls with either an increase or a decrease in pressure.

Animals↗
PubMed1994

Concentrations of corticotropin-releasing hormone, norepinephrine, MHPG, 5-hydroxyindoleacetic acid, and tryptophan in the cerebrospinal fluid of alcoholic patients: serial sampling studies.

Abnormalities in corticotropin-releasing hormone (CRH) secretion, noradrenergic neurotransmission, and serotonergic activity in the central nervous system (CNS) have all been hypothesized to exist in alcoholic patients, as have abnormalities in hypothalamic-pituitary adrenal function. To test these hypotheses, we continuously sampled cerebrospinal fluid (CSF) from alcoholic patients after 38-124 days of abstinence and from normal volunteers via a flexible, indwelling lumbar subarachnoid catheter and measured CRH, norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), tryptophan, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations at 10-min intervals, from 11:00 through 17:00 h. The spinal canal catheter was inserted at approximately 08:00 h. Serial plasma ACTH, cortisol, and NE concentrations were also measured. A mixed liquid meal was consumed at 13:00 h. CSF CRH concentrations were lower in alcoholic patients than in normal volunteers (26 +/- 15 vs. 60 +/- 30 pg/ml, respectively, p < 0.05 by ANOVA), as were CSF NE levels (0.33 +/- 0.09 vs. 1.15 +/- 0.51 pmol/ml, respectively, p < 0.01). Plasma NE and CSF MHPG levels were normal in the alcoholic patients. CSF tryptophan and 5-HIAA and plasma ACTH and cortisol concentrations did not differ between the groups. These studies extend our finding of reduced spinal canal CSF CRH concentrations in depressed patients to abstinent chronic alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed2002

Variation in reproductive outcomes for captive male rhesus macaques (macaca mulatta) differing in CSF 5-hydroxyindoleacetic acid concentrations.

In rhesus macaque males, lower than average cerebrospinal fluid (CSF) concentrations of the principle metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), have been linked to impulsivity, involvement in escalated aggression, failure to elicit consort relationships, production of fewer sperm plugs, and a relatively early age of mortality. Given these potential fitness costs, we performed two studies aimed at elucidating the effects of CSF 5-HIAA on reproduction. Study 1 retrospectively evaluated over a four-year period, the relative reproductive outcome for pairs of adult male rhesus macaques (n = 15) who lived in social groups and who differed in concentrations of CSF 5-HIAA. Study 2 examined the relationship between CSF 5-HIAA and sperm motility and density (n = 12), as a potential mechanism for maintaining variability in CSF 5-HIAA. For Study 1, an average measure from two CSF 5-HIAA samples was calculated for the two males who were present during the time when conception most likely took place (offspring birth date -165 +/- 14 days). Within-pair comparisons of CSF 5-HIAA concentrations between the sire and the non-successful male were drawn for each of the 72 offspring in the study. We found that while sires were typically the male with relatively higher CSF 5-HIAA within the pair, there were no absolute differences in CSF 5-HIAA between males who sired at least one offspring (sires) and those who failed to reproduce (non-sires). Furthermore, while absolute age was not predictive of reproductive outcome, sires with relatively high CSF 5-HIAA also tended to be also relatively older than their competitors. By contrast, for the males with relatively low CSF 5-HIAA who reproduced, sires were relatively younger than the non-sires. These differences in reproductive outcome for males differing in CSF 5-HIAA could not be explained by variability in sperm quantity or quality as we did not find evidence of a relationship between CSF 5-HIAA and either sperm measure. The results of this study suggest that as serotonergic function affects many aspects of behavior and survivorship, it might also be associated with reproductive outcome and different life-history strategies for males differing in concentrations of CSF 5-HIAA.

Animals↗
PubMed1981

In vivo measurements by differential pulse voltammetry of extra-cellular 5-hydroxyindoleacetic acid in the rat brain.

The use of differential pulse voltammetry, performed with electrochemically treated carbon fiber electrodes, enables us to detect in vitro or in vivo, in the striatum of anaesthetized rats, an oxidation peak (3) at a potential of + 300 mV. Electrolytic or 5-7-dihydroxytryptamine lesions of the medial forebrain bundle are followed by a decrease of 59 and 62% respectively of this peak. Biochemical measurements are significantly correlated with the measured peak (3) and decreases. Thus, peak (3) increases obtained after injection of L-tryptophan and/or Reserpine, as well as the decreases observed after injection of Clorgyline or 3-hydroxybenzylhydrazine, confirm that peak (3) is dependent upon 5-hydroxyindoleacetic acid concentration. The detection of a peak (3) in the cerebrospinal fluid and its increase after injection of Probenecid reinforce this conclusion.

5,7-Dihydroxytryptamine↗
PubMed2002

Serotonin, 5-hydroxyindoleacetic acid and serotonin transporter in blood peripheral lymphocytes of patients with generalized anxiety disorder.

Several immune system modifications have been reported in pathological anxiety, such as generalized anxiety, panic and obsessive-compulsive disorders. Since serotonin transporter is a marker of peripheral blood lymphocytes and it is modified in major depression, the aim of the present work was to evaluate this transporter by the binding of [3H]paroxetine to membrane preparations of blood peripheral lymphocytes from control subjects and patients with generalized anxiety disorder. The number of transporters and the affinity for the ligand did not differ among the two groups. Serotonin and 5-hydroxyindoleacetic acid (5HIAA) were determined in platelet-rich and -poor plasma, and in lymphocytes. Nonsignificant changes were found in the patients as compared to controls. However, there was a significant positive correlation between serotonin concentration in platelet-poor plasma and in lymphocytes in the patients, but not in the controls. This finding might be an indication of a poor regulation of the transporter function by which serotonin plasma concentration might influence lymphocyte serotonin concentration. Previous results indicate that serotonin transporter is reduced in these cells in major depression disorder; however, in generalized anxiety disorder, the number of transporters was not modified, although the functional efficiency of serotonin transporter might be altered.

Adult↗
PubMed1976

Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs.

In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects.

Adult↗
PubMed2001

Cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in HIV-1 infection.

Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1- control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1- group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck's Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.

Adult↗
PubMed1993

Treatment of pregnant alcohol-consuming rats with buspirone: effects on serotonin and 5-hydroxyindoleacetic acid content in offspring.

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5-HT) and 5-HT1A receptors for the normal development of 5-HT containing neurons, we initiated studies to determine whether administration of a 5-HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring. Female, Sprague-Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol-associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5-HT and/or 5-HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age-matched offspring of buspirone-treated, ethanol-fed rats. In contrast, the 5-HT and 5-HIAA deficiency in the somatosensory cortex of 19-day-old offspring of ethanol-fed rats was not corrected by in utero buspirone treatment. These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5-HT content in ethanol-exposed rats and may potentially be overcome by in utero treatment with a 5-HT1A agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Extracellular serotonin and 5-hydroxyindoleacetic acid in hypothalamus of the unanesthetized rat measured by in vivo dialysis coupled to high-performance liquid chromatography with electrochemical detection: dialysate serotonin reflects neuronal release.

In vivo dialysis coupled to high-performance liquid chromatography with electrochemical detection (HPLC-EC) was used for measurement of extracellular serotonin (5-HT) in the hypothalamus of unanesthetized, unrestrained rats. A series of experiments was carried out to determine if 5-HT in the dialysis solution was released from nerve terminals. Fenfluramine, a 5-HT-releasing drug and fluoxetine, a 5-HT-reuptake inhibitor, both significantly increased extracellular 5-HT. Elevating potassium concentration in the dialysis solution also significantly increased 5-HT. Reciprocally, 5-HT was significantly reduced to about half of control levels with either local administration of tetrodotoxin, zero calcium dialysis solution, or systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A agonist that suppresses 5-HT neuronal activity via activation of the somatodendritic autoreceptor. In addition, 5-HT levels were elevated during the dark portion of the light-dark cycle, a period when rats are more active. Changes in extracellular 5-hydroxyindoleacetic acid (5-HIAA) rarely followed changes in 5-HT. The results indicate that 5-HT in the dialysis solution, but not 5-HIAA, was a reliable measure of depolarization-induced release of 5-HT from nerve terminals. This is the first report establishing the reliability of in vivo dialysis coupled to HPLC-EC for measurement of synaptically released 5-HT.

Animals↗
PubMed2003

Higher plasma 5-hydroxyindoleacetic acid levels are associated with SSRI-induced nausea.

We investigated the association between selective serotonin reuptake inhibitors (SSRIs; paroxetine or fluvoxamine) and nausea with regard to plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels. Forty-eight patients meeting the DSM-IV criteria for major depressive disorder and treated with paroxetine or fluvoxamine participated in this study. p5-HIAA levels after SSRI administration were significantly higher in the nausea group than those in the nonnausea group (nausea group: 8.0 +/- 4.6 ng/ml; nonnausea group: 3.6 +/- 2.2 ng/ml; p < 0.01). On the other hand, no significant difference was found between the nausea and nonnausea group in terms of p5-HIAA levels before each drug administration. These results suggest that SSRI-induced nausea is associated with serotonergic hyperactivity in the gastrointestinal tract.

Acetophenones↗
PubMed1988

Evaluation of sample work-up methods and internal standards for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in brain by HPLC with electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection is described for the determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brain. Results of studies on sample work-up methods and on the use of various internal standards are reported. The reproducibility of determination of 5-HT and 5-HIAA in two regions of rabbit brain has been evaluated.

Journal Article↗