Parallel variation of homovanillic acid and 5-hydroxyindoleacetic acid in ventricular cerebrospinal fluid of man.
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The investigated group comprised 35 patients where clinical examination revealed focal cerebral ischaemia in the area of the a. cerebri media. In the group of elderly patients above 60 years, as compared with controls, the homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) concentration in cerebrospinal fluid was elevated. In the group of patients under 60 years no changes in the concentration of these metabolites were found. In older patients the increased level of metabolites in cerebrospinal fluid persisted also after three days following the attack, while in younger patients the elevated HVA and 5-HIAA levels were found only in specimens collected up to three days.
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The in vivo effect of a single oral dose of 100 mg (+)-dihydromethysticin/kg body weight on striatal and cortical tissue concentrations of dopamine, serotonin, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid, as well as the dopamine and serotonin turnover, was tested in rats. Additionally, other rats were fed with a (+/-)-kavain containing food over a period of 78 days in order to calculate the influence of a chronic treatment with kavapyrones on the neurotransmitters. The results of the present in vivo study clearly demonstrate that neither (+)-dihydromethysticin in a high single dose, nor (+/-)-kavain chronically administered, altered the dopaminergic or serotonergic tissue levels in rats significantly.
A method using reversed-phase ion-pair high-performance liquid chromatography with electrochemical detection for the simultaneous determination of tryptophan (TRP), 3,4-dihydroxyphenylalanine (DOPA), and their metabolites in whole brain, small-brain parts, and cerebrospinal fluid of rats has been developed. The sample preparation requires only homogenization in perchloric acid and centrifugation before injection onto the column. With a LiChrosorb RP-18 (10 micrometer) column and a mobile phase consisting of a phosphate (NaH2PO4, 0.1 M)-methanol mixture with octylsulfonate (2.6 x 10(-3) M) at pH 3.35 and 26 degrees C, the separation of DOPA, dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 4-hydroxy-3-methoxyphenylalanine, TRP, 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindoleacetic acid was achieved. The method has been applied to study the effect of alpha-monofluoromethyldopa alone and in combination with L-DOPA or L-5-HTP, on the catechol and 5-OH indole levels in brain and CSF of the rat.
The effects of swimming stress on dopaminergic and serotonergic neurons were studied by an in vivo voltammetry technique. 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels in rat striatum were measured by differential pulse voltammetry with an electrochemically treated carbon fiber electrode. Exposure to swimming stress for 1 to 10 min to the animal increased the DOPAC and 5-HIAA peaks, which depended on the length of stress. Pretreatment of the rats with diazepam (10 mg/kg, i.p.) prevented completely the stress-induced increase in DOPAC levels but only partially reduced the increase in 5-HIAA levels.
Differential pulse voltammetry with a newly devised carbon fiber electrode was used to study the nature of striatal electrochemical signals. Voltammograms recorded from the striatum of unanesthetized rats usually yielded the combined oxidation peak (1 + 2) and peak 3. Peaks 1 and 2 could be separated by eliminating peak 1 for ascorbate by electrochemical oxidation in the brain to allow clear monitoring of peak 2 at + 120 mV for catechols and peak 3 at + 270 mV for indoles. The changes in the oxidation potentials and the amplitudes of peaks 2 and 3 corresponded to those of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in vivo because: the oxidation potentials of peak 2 (+ 120 mV) and peak 3 (+ 270 mV) coincided with those of DOPAC and 5-HIAA in vitro; increases in the heights of peaks 2 and 3 were observed after micro-infusion of DOPAC and 5-HIAA, respectively, into the striatum; and peak 2 height increased after injection of haloperidol and gamma-butyrolactone and decreased after amphetamine and pargyline, while peak 3 amplitude increased following injection of gamma-butyrolactone, probenecid and 5-hydroxytryptophan and decreased after pargyline. Thus, the in vivo voltammetry method enabled simultaneous and stable monitoring of the dynamic changes in DOPAC and 5-HIAA levels in the brains of freely moving rats.
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Concentrations of tryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in brain and plasma, as well as plasma amino acid composition, were measured after 1-h foot shock. Stress induced a rise in both plasma and brain 5-HIAA, whereas 5-HT concentration was found to be increased only in plasma. A prominent rise in brain tryptophan was observed, whereas in plasma, foot shock caused a significant increase only in tryptophan level. Concentrations of other amino acids were found to be either decreased or unchanged. Ratio of tryptophan to the other long-chain neutral amino acids increased significantly following foot shock. It is possible that stress-related changes in 5-HT turnover are due to increased plasma tryptophan, in turn causing a rise in brain tryprophan, necessary to cope with enhanced 5-HT metabolism, reflected as a rise in 5-HIAA levels.
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