Serotonin 5-hydroxyindoleacetic acid level

Boonen G, Ferger B, Kuschinsky K, Haberlein H. (1998). In vivo effects of the kavalactones (+)-dihydromethysticin and (H-/-)-kavain on dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid levels in striatal and cortical brain regions. Planta Med. 64(6) 507-10. Boonen G, Haberlein H. (1998). Influence of genuine kavalactone enantiomers on the GABA-A binding site. Planta Med. 64(6) 504-6. 

Serotonergic function has been investigated by using multiple methods. Assaying the major metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) has been widely used (Ch. 13). This method assumes that CSF 5-HIAA is related to brain serotonin activity. This premise is supported by the rostral-caudal concentration gradient of CSF 5-HIAA and the observation in postmortem studies that CSF 5-HIAA correlates with levels of 5-HIAA in prefrontal cortex [16], both of which suggest that CSF 5-HIAA is a reasonable index of prefrontal serotonin turnover. ... 

Mice exposed for 28 days to phenol in drinking water exhibited a significant reduction in dopamine level in the corpus striatum at the 1.8 mg/kg/day dose, and significantly decreased levels of norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in the hypothalamus at the 6.2 mg/kg/day dose (Hsieh et al. 1992). Levels of neurotransmitters in other brain regions were also significantly altered at higher doses of phenol. 

In essentially all species of animals, including humans, serotonin is important in aggression (Kravitz, 2000). Relationships between CSF concentrations of a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and human aggression were described in As-berg et al. s landmark study (1976), which showed a bimodal distribution among depressed patients. A meta-analysis of 27 studies, involving 1202 psychiatric patients, showed an association between attempted suicide and low levels of CSF 5-HIAA (Lester, 1995). 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

The first neurochemical evidence of a disturbed serotonin function in cognition came from the changes in serotonin and/or 5-hydroxyindoleacetic acid (5-HIAA) levels in a number of forebrain nuclei, the temporal and cingulate cortex, hippocampus, and other areas of the brain taken at autopsy from patients with senile dementia of the Alzheimer s type (Adolfsson et al. 1978 Arai et al. 1984 D. M. Bowen et al. 1979, 1983 A. J. Cross et al. 1983 Winblad et al. 1982). The depletions are regionally selective reductions in se-... 

There is also evidence of low levels of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of impulsive individuals. We might hypothesize that, in a nonresponsive, impulsive patient, diminished serotonin plays a role in the pathophysiology. This hypothesis could now be tested and simultaneously serve as the foundation for a pathophysiologically based treatment by choosing therapies specific for various components of this system. For example, the 5-HT agonist buspirone might be tried, because there is limited evidence from open trials that it has antiaggressive properties. 

The hypothesis that SSRIs work in OCD by a serotonergic mechanism is also supported by studies showing a strong positive correlation between improvement in obsessive-compulsive symptoms during clomipramine treatment and drug-induced decreases in cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin concentrations. Thus, peripheral markers of 5HT function link the symptomatic improvement in OCD symptoms produced by SSRIs to changes in 5HT function. However, these markers do not consistently highlight a 5HT abnormality in untreated patients with OCD,... 

With regard to neurotransmitters, we found no significant difference in the levels of norepinephrine, 3,4-dihydrophenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, homovanilinic acid, and serotonin in the frontal cortex, the hippocampus, and the striatum between conventional rats fed the safflower-oil diet and those fed the perilla-oil diet. The acetylcholine (Ach) level was very high in the striatum, but these diets had no effect on the Ach levels in brain regions (Fig. 6). In stroke-prone spontaneously hypertensive rats, DHA supplementation increased Ach levels in the frontal cortex and the hippocampus compared with those fed the safflower-oil diet (Minami, 1997a,b). 

Knapp et al.21 reported that the levels of forebrain tryptophan, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and hydroxylase cofactor (BH4) were comparable in two experimental mouse strains (A/J and C57B1/6J), despite two- to three-fold differences in vitro in the relative activities of forebrain and midbrain tryptophan-5-monoxygenase. The enzyme activities did not differ with respect to Km for cofactor at saturating levels, but manifested different degrees of cooperativity with respect to cofactor when examined with BH4 concentrations within a physiological range. 

Regarding the pharmacological effects of theanine, previous reports have indicated a reduction in blood pressure in spontaneously hypertensive rats, a relief from convulsions induced by caffeine, and an influence on the brain levels of norepinephrine, serotonin, 5-hydroxyindoleacetic acid, and dopamine. Moreover, oral intake of theanine results in the generation of a-electric waves in the occipital and parietal regions of the human brain Theanine-induced inhibition of glutamate transporter enhances the activity of an antitumor agent. It increased doxorubicin (DOX)-induced antitumor activity, and confirmed that this action contributed to the increase in the DOX concentration in a tumor with inhibition of the DOX efflux from tumor cells. ... 

It has been shown that theanine has numerous health effects, ranging from prevention of neuronal death to reduction of tumor growth, enhancement of antitumor activity of chemotherapeutic agents, and reduction of hypertension and blood pressure. Moreover, theanine relieves excitation induced by caffeine ingestion and influences the brain levels of norepinephrine, serotonin, 5-hydroxyindoleacetic acid, and dopamine. In addition, ethylamine, a major metabolite of theanine, has been found to boost immune response. 

Evidence against this serotonin theory includes the fact that low levels of 5HIAA (5-hydroxyindoleacetic acid, a metabolite of serotonin) are seen even in patients who have recovered and in some patients with mania. 

Serotonin has been found to influence sleeping, the regulation of body temperature, and sensory perception, but its exact role in mental illness is not yet clear. Unusually low levels of 5-hydroxyindoleacetic acid, a product of serotonin utilization, are characteristically found in the spinal fluid of victims of violent suicide. Drugs that mimic serotonin are sometimes used to treat depression, anxiety, and obsessive-compulsive disorder. Serotonin blockers are used to treat migraine headaches and relieve the nausea that accompanies cancer chemotherapy. A better understanding of the biochemistry of the brain may lead to better medications for treating various forms of mental illness. 

The determination of catecholamines requires a highly sensitive and selective assay procedure capable of measuring very low levels of catecholamines that may be present. In past years, a number of methods have been reported for measurement of catecholamines in both plasma and body tissues. A few of these papers have reported simultaneous measurement of more than two catecholamine analytes. One of them utilized lised UV for end-point detection and the samples were chromatographed on a RP phenyl analytical column. The procedure was slow and cumbersome because ofdue to the use of a complicated liquid-hquid extraction and each chromatographic run lasted more than 25 min with a detection Emit of 5-10 ng on-column. Other sensitive HPLC methods reported in the hterature use electrochemical detection with detection limits 12, 6, 12, 18, and 12 pg for noradrenaline, dopamine, serotonin, 5-hydroxyindoleacetic acid, and homovanillic acid, respectively. The method used very a comphcated mobile phase in terms of its composition whilewhilst the low pH of 3.1 used might jeopardize the chemical stabihty of the column. Analysis time was approximately 30 min. Recently reported HPLC methods utilize amperometric end-point detection. " ... 

Fig. 2.3. Diagnostic flow-chart in the differentiation of defects of biogenic amine neurotransmitter metabolism. The correct differential diagnosis depends on the pattern of amines and their metabolites in either urine, CSF or plasma. represents increased values, [ represents lowered values. 5HIAA 5-hydroxyindoleacetic acid HVA homovanillic acid 5HT serotonin 30MD 3-0-methyldopa DOPAC dihydroxyphenylacetic acid 3MT 3-methoxytyramine NMN norme-tanephrine VMA vanillylmandelic acid DOPS dihydroxyphenylserine MHPG 3-methoxy-4-hydroxyphenylglycol Y yes N no. Plasma and CSF levels have not been analysed but they probably reflect those seen in urine. For interpretation of quantitative results see pathological values.

---