How can serotonin levels be measured

Return to work and depressive symptoms in young stroke survivors. Vysioneer receives FDA clearance for tumour auto-contouring solution 9 April Return to work and depressive symptoms in young stroke survivors 4 November This figure adapted from [ 23 ]. In the early s, liquid chromatography LC with an electrochemical detector ED had been widely used for the measurement of neurochemicals [ 5 ]. The first 5-HT project that I worked with was to develop a method for measuring 5-HT concentration in chicken brain tissue [ 6 ].

An isocratic LC-ED for the determination of L-3,4-dihydroxyphenylalanine, dopamine, norepinephrine, epinephrine, 5-HT, and their major metabolites, 3,4-dihydroxyphenylacetic acid, 4-hydroxymethoxyphenylacetic acid, and 5-hydroxyindoleacetic acid in chicken brain tissue was developed in our lab. The method was applied to study the influence of food restriction on the concentration of 5-HT and other monoamine neurotransmitters in different brain areas, known to be involved in the feeding and reproductive behavior of female broiler chickens.

Supernatant was injected onto LC-ED, and over micro-punched tissue samples from ad libitum fed and food-restricted female broiler chickens were analyzed. Although the concentration of monoamines in the brain is not high, multiple tissue micropunches made enough amount of monoamine and 5-HT to match the sensitivity of the assay. Our results provided a possible role for catecholamines and indolamines in the altered feeding and reproductive behavior of the broiler chicken [ 6 ]. To finish my Ph.

The role of monoaminergic neuromodulators in the reorganization of cortical topography following limited sensory deprivation in the adult cat was investigated in this study [ 8 ]. The total concentrations of dopamine, noradrenaline, 5-HT, and their major metabolites were measured in the visual cortex of both control and experimental animals using this microbore LC-ED method.

The sensory deprivation cats were subjected to a binocular retinal lesion corresponding to the central 10 degrees of vision and sacrificed 2 weeks post-lesion. The deprivation was confirmed in area 17 by measuring immediate-early gene if messenger RNA expression. The total concentration of 5-HT was significantly lower in the deprived cortex, and the metabolite of 5-HT, 5-hydroxyindoleacetic acid, was significantly higher in the nondeprived cortex than in deprived cortex and normal cortex.

The levels of noradrenaline and dopamine were significantly higher in the nondeprived cortex of retinal lesion cats than in the deprived cortex of retinal lesion cats and the cortex of normal animals. This pattern follows the release of the excitatory neurotransmitter glutamate under the same conditions. These results suggest that the modulation of 5-HT, noradrenaline, and dopamine is regulated by visual afferent activity [ 8 ]. To switch my scientific career to the pharmaceutical industry, I joined the CNS drug discovery team for making a new generation dual function SSRI [ 9 ] for depression treatment.

In vivo microdialysis has been extensively used to document the changes of extracellular level of 5-HT in the rat brain after administration of fluoxetine [ 11 ]. Animals were allowed at least 3 days to recover from surgery prior to experimentation. Samples were collected every 60 min. Microdialysates were analyzed by LC-ED. Separation was performed on a C18 column. All values for microdialysis studies were calculated as percentage change at each time point compared with the average of three baseline values.

Pharmacokinetic PK characterization and in vivo pharmacological properties of new chemical entities are important components during lead compound selection and optimization in the drug discovery process.

When dealing with compounds targeting the central nervous system CNS , biophase PK may differ significantly from plasma PK, because blood-brain barrier BBB transport and brain distribution often do not occur instantaneously and to a full extent. In vivo microdialysis technique can be used to collect not only the extracellular endogenous substances but also the extracellular free drug in the same local interstitial environment, which may reflect the amount of drug available at the pharmacological target.

However, the application of this technique was highly limited by the lack of the proper sensitive analytical methods to determine the endogenous substance and exogenous drug.

The mass spectrometer has minimal baseline drift and can be equilibrated very rapidly. The World Health Organization WHO estimates that more than million individuals of all ages suffer from depression [ 14 ].

SSRIs have been the drugs for depression treatment. These drugs increase 5-HT levels in the synaptic cleft by inhibiting its reuptake into the presynaptic neuron through blockade of the SERT.

No single test can confirm a serotonin syndrome diagnosis. Your doctor will diagnose the condition by ruling out other possibilities.

Your doctor will likely begin by asking about your symptoms, medical history and any medications you're taking. Your doctor will also conduct a physical examination. To make sure your symptoms are caused by serotonin syndrome and not due to another cause, your doctor may use tests to:.

A number of conditions can cause symptoms similar to those of serotonin syndrome. Minor symptoms can be caused by several conditions, while moderate and severe symptoms similar to those of serotonin syndrome could be caused by:.

Your doctor may order additional tests to rule out other causes of your symptoms. Tests may include:. Drugs that control heart rate and blood pressure. These may include esmolol Brevibloc or nitroprusside Nitropress to reduce a high heart rate or high blood pressure.

If your blood pressure is too low, your doctor may give you phenylephrine Vazculep or epinephrine Adrenalin, Epipen, others. Milder forms of serotonin syndrome usually go away within 24 to 72 hours of stopping medications that increase serotonin, and by taking medications to block the effects of serotonin already in your system if they're needed. However, symptoms of serotonin syndrome caused by some antidepressants could take several weeks to go away completely.

A unified theory of affective disorders can only be achieved if we consider different imaging methods and also take into account both animal and human histological data. In the future it may be worthwhile to develop the tools to study both receptor density and 5-HT synthesis, and this will hopefully yield a better and more complete understanding of the processes involved in the pathophysiology of affective disorders. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited.

National Center for Biotechnology Information , U. Published online Nov Anniek K. Visser , 1 Aren van Waarde , 1 Antoon T. Willemsen , 1 Fokko J. Bosker , 2 Paul G. Luiten , 3 Johan A. Kema , 4 and Rudi A. Dierckx 1, 5. Antoon T. Fokko J. Paul G. Johan A. Ido P. Rudi A. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Jun 17; Accepted Nov 1. This article has been cited by other articles in PMC.

Abstract The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors each with their particular distribution patterns , specific reuptake mechanisms and synthetic processes.

Introduction Serotonergic innervations are widely spread throughout the brain with cell bodies of origin lying in the dorsal DRN or median MRN raphe nucleus, and a column of raphe nuclei in lower brainstem regions, projecting to basically all divisions of the brain and spinal cord Fig.

Open in a separate window. Table 1 PET tracers used for research on serotonergic neurotransmission. MZ Herth et al. However, this method has also many drawbacks [ 31 ]: A lumbar puncture is invasive and often experienced as unpleasant. Recent technologies: radiopharmaceuticals for measuring serotonin synthesis Recent technologies allow research in living animals and humans.

Preclinical data Kinetic modelling and validation The first studies employed AMT labelled with 3 H and 14 C to perform autoradiography in rats. Effect of pharmacological challenges Studies with 14 C-labelled AMT in experimental animals using autoradiographic techniques after various interventions and brain lesions indicated that AMT could detect changes in the rate of 5-HT synthesis see reviews by [ 31 , 54 ]. Preclinical PET studies Although the above-mentioned studies may provide important insights regarding physiological processes in animals, autoradiography does not take individual rate constants into account.

Clinical data Eventually a tracer should have the ability to visualize physiological processes in humans, in order to clarify the pathophysiology of disease and to be employed in routine clinical practice. Neuroendocrine tumour imaging [ 11 C]5-HTP is mainly used for the detection of neuroendocrine tumours and not for brain imaging.

Preclinical data In , an initial preclinical study with [ 11 C]5-HTP for measuring cerebral 5-HT synthesis was performed in rhesus monkeys [ ]. Discussion The serotonergic system is complex, influencing many other neurotransmitter systems and behavioural functions.

Conclusion We have reviewed several techniques for the evaluation of serotonin synthesis. Conflicts of interest None. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited. References 1. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Pharmacol Rev. From inflammation to sickness and depression: when the immune system subjugates the brain.

Nat Rev Neurosci. J Chem Soc Perkin Trans. Eur J Pharmacol. A new method to measure brain serotonin synthesis in vivo. Theory and basic data for a biological model. J Cereb Blood Flow Metab. Nucl Med Biol. Eur J Nucl Med. Synthesis and in vivo evaluation of a novel 5-HT1A receptor agonist radioligand [O-methylC]2- 4- 4- 2-methoxyphenyl piperazinyl butyl methyl-1,2,4-triazine-3,5 2H,4H dione in nonhuman primates. Development of fluorinelabeled 5-HT1A antagonists. J Med Chem. Fluorinealtanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats.

J Nucl Med. Life Sci. Characterization in the primate brain. Cortical trapping of alpha-[ 11 C]methyl-l-tryptophan, an index of serotonin synthesis, is lower in females than males.

Curr Top Med Chem. Rapid and sensitive method for measuring norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites in rat brain by high-performance liquid chromatography. Differential effect of probenecid, haloperidol and yohimbine on the concentrations of biogenic amines and metabolites in various regions of rat brain.

J Chromatogr. J Neural Transm. Stenfors C, Ross SB. Changes in extracellular 5-HIAA concentrations as measured by in vivo microdialysis technique in relation to changes in 5-HT release. Psychopharmacology Berl ; 2 — Diksic M, Young SN.

Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem. Sneddon JM. Blood platelets as a model for monoamine-containing neurones. Prog Neurobiol. Stahl SM. The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders.

Arch Gen Psychiatry. Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

Exp Brain Res. Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism. Serotonin in human lumbar cerebrospinal fluid: a reassessment.

Serotonin metabolism in depression: clinical application of the probenecid test. Int Pharmacopsychiatry. Central serotonin metabolism and frequency of depression. Psychiatry Res. Depression, suicide and the metabolism of serotonin in the brain. J Affect Disord. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy.

Denosologization of biological psychiatry or the specificity of 5-HT disturbances in psychiatric disorders. Comparison of cortical 5-HT2A receptor binding in bulimia nervosa patients and healthy volunteers. Am J Psychiatry. Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide.

Decreased 5-HT2a receptor binding in patients with anorexia nervosa. Brain serotonin content: physiological dependence on plasma tryptophan levels. Fernstrom JD. Effects on the diet on brain neurotransmitters. Analysis of [C]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo.

Model of brain serotonin metabolism. Physiological interpretation. Am J Physiol. Alpha-methyltryptophan: effects on synthesis and degradation of serotonin in the brain.

A practical autoradiographic method tested in normal and lithium-treated rats. Diksic M. J Chem Neuroanat. Determination of the lumped constant for the alpha-methyltryptophan method of estimating the rate of serotonin synthesis. Labelled alpha-methyl-L-tryptophan as a tracer for the study of the brain serotonergic system.

J Psychiatry Neurosci. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Biochemical and autoradiographic measurements of brain serotonin synthesis rate in the freely moving rat: a reexamination of the alpha-methyl-L-tryptophan method.

The suitability of [11C]-alpha-methyl-L-tryptophan as a tracer for serotonin synthesis: studies with dual administration of [11C] and [14C] labeled tracer. Chugani DC, Muzik O.