Effects of the Diet and other Metabolic Phenomena on Brain Tryptophan Uptake and Serotonin Synthesis

The tracer [11C]-α-methyl-L-tryptophan (αMTP) has been used to measure brain serotonin synthesis rates with positron emission tomography (PET). To address questions about the accuracy of the kinetic model, [14C]αMTP was used to directly measure conversion to [14C]-α-methyl-serotonin (αM5HT) in monkeys that had been previously studied with PET and [11C]αMTP. Four male, fasted, isoflurane-anesthetized rhesus monkeys were studied with [11C]αMTP and PET. Immediately after the initial 3-hour scan, a second dose of [11C]αMTP was coinjected with 1 mCi of [14C]αMTP, and additional PET data were collected. Approximately 90 minutes after the second αMTP administration, the animals were killed with an overdose of phenobarbital, and brain samples from 21 regions were taken and analyzed by HPLC. Minimal conversion of αMTP to αM5HT occurred; HPLC analysis of 14C radioactivity showed that greater than 96% of the total counts were in fractions corresponding to the αMTP peak. Brain concentrations of serotonin, tryptophan, 5-hydroxyindole-3-acetic acid, and αMTP also were determined fluorometrically using external quantification. Patlak plots generated from PET images acquired over 3 hours showed no time period of linear increase, and final slopes were not significantly different from zero, consistent with the finding of minimal conversion to [14C]αM5HT. These data indicate that in the 3-hour period after injection, [11C]αMTP is acting predominantly as a tracer of tryptophan uptake, not serotonin synthesis.

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The ingestion of different dietary proteins by humans induces large changes in the plasma tryptophan ratio, a predictor of brain tryptophan uptake and serotonin synthesis

Clinical Nutrition ◽

10.1016/j.clnu.2012.11.027 ◽

2013 ◽

Vol 32 (6) ◽

pp. 1073-1076 ◽

Cited By ~ 19

Author(s):

John D. Fernstrom ◽

Kathryn A. Langham ◽

Lyndsey M. Marcelino ◽

Zoë L.E. Irvine ◽

Madelyn H. Fernstrom ◽

...

Keyword(s):

Dietary Proteins ◽

Serotonin Synthesis ◽

Plasma Tryptophan ◽

Tryptophan Uptake

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The effects of chlorpromazine on serum tryptophan, brain tryptophan uptake and brain serotonin synthesis in the rat

Biochemical Pharmacology ◽

10.1016/0006-2952(76)90408-1 ◽

1976 ◽

Vol 25 (15) ◽

pp. 1743-1746 ◽

Cited By ~ 13

Author(s):

David A. Bender

Keyword(s):

Brain Serotonin ◽

Serotonin Synthesis ◽

Tryptophan Uptake

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Dietary intake of tryptophan tied emotion-related impulsivity in humans

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000608 ◽

2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Florian Javelle ◽

Descartes Li ◽

Philipp Zimmer ◽

Sheri L. Johnson

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Food Intake ◽

Essential Amino Acid ◽

Food Habits ◽

Psychological Disorder ◽

Serotonin Synthesis ◽

Amino Acid Tryptophan ◽

Pass Through ◽

Three Factor

Abstract. Emotion-related impulsivity, defined as the tendency to say or do things that one later regret during periods of heightened emotion, has been tied to a broad range of psychopathologies. Previous work has suggested that emotion-related impulsivity is tied to an impaired function of the serotonergic system. Central serotonin synthesis relies on the intake of the essential amino acid, tryptophan and its ability to pass through the blood brain barrier. Objective: The aim of this study was to determine the association between emotion-related impulsivity and tryptophan intake. Methods: Undergraduate participants (N = 25, 16 women, 9 men) completed a self-rated measure of impulsivity (Three Factor Impulsivity Index, TFI) and daily logs of their food intake and exercise. These data were coded using the software NutriNote to evaluate intakes of tryptophan, large neutral amino acids, vitamins B6/B12, and exercise. Results: Correlational analyses indicated that higher tryptophan intake was associated with significantly lower scores on two out of three subscales of the TFI, Pervasive Influence of Feelings scores r = –.502, p < . 010, and (lack-of) Follow-Through scores, r = –.407, p < . 050. Conclusion: Findings provide further evidence that emotion-related impulsivity is correlated to serotonergic indices, even when considering only food habits. It also suggests the need for more research on whether tryptophan supplements might be beneficial for impulsive persons suffering from a psychological disorder.

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In vitro screen of inhibitors of rat brain serotonin synthesis

Canadian Journal of Biochemistry ◽

10.1139/o69-078 ◽

1969 ◽

Vol 47 (5) ◽

pp. 501-506 ◽

Cited By ~ 26

Author(s):

E. G. McGeer ◽

D. A. V. Peters

Keyword(s):

Rat Brain ◽

Tryptophan Hydroxylase ◽

Inhibitory Effect ◽

Complexing Agents ◽

Serotonin Synthesis ◽

Structural Requirements ◽

Class A ◽

Numerous Data ◽

Comparison Of The Results

Over 700 compounds were screened at 10−4 M concentration as inhibitors of the conversion of L-tryptophan-14C to serotonin-14C in crude rat brain homogenates. Most of the compounds had little or no inhibitory effect. Those with strong inhibitory properties were tested as inhibitors of 5-hydroxytryptophan decarboxylase and, if active on the decarboxylase, were assayed as tryptophan hydroxylase inhibitors. Except for a few oxidizing and complexing agents and for some substituted p-phenylenediamines, the compounds found to inhibit tryptophan hydroxylase by >50% belonged to the three types of inhibitors already known, i.e. catechols, phenylalanine and ring-substituted phenylalanines, and 6-substituted tryptophans. The numerous data in this screen make possible some comments as to the structural requirements for activity within each class. A comparison of the results on tryptophan hydroxylase with data on tyrosine hydroxylase inhibition in similar homogenates makes it clear that two separate, if somewhat similar, enzymes are involved.

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Serotonin depletion reduces both acquisition and expression of context-conditioned fear

Acta Neuropsychiatrica ◽

10.1017/neu.2021.3 ◽

2021 ◽

pp. 1-8

Author(s):

S. Melker Hagsäter ◽

Robert Pettersson ◽

Axel Holmäng ◽

Elias Eriksson

Keyword(s):

Unconditioned Stimulus ◽

Memory Consolidation ◽

Clinical Studies ◽

Conditioned Fear ◽

Sprague Dawley ◽

Serotonin Synthesis ◽

Synthesis Inhibitor ◽

Serotonin Depletion ◽

Sprague Dawley Rats ◽

The Impact

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.

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The role of tryptophan in hepatic encephalopathy

Acta Neuropsychiatrica ◽

10.1017/s0924270800033810 ◽

1993 ◽

Vol 5 (4) ◽

pp. 71-75

Author(s):

C. Aaldijk ◽

W.W. Van Den Broek ◽

R.C. Van Der Mast

Keyword(s):

Hepatic Encephalopathy ◽

Clinical Picture ◽

Serotonergic System ◽

Pathogenetic Mechanisms ◽

Research Findings ◽

Glutamine Synthesis ◽

The Brain ◽

Tryptophan Uptake

SummaryIn this review the most important hypotheses for the occurrence of the clinical picture of hepatic encephalopathy are discussed. As possible pathogenetic mechanisms are raised: dysfunction of the serotonergic system due to an increased tryptophan uptake in the brain, an elevated intracerebral ammoniac concentration and glutamine synthesis, and a heightened intracerebral GABA-activity.The dysregulation of the serotonergic system as a consequence of the increased intracerebral tryptophan uptake is described as one of the most important pathogenetic mechanisms. The elevated intracerebral ammoniac concentration and the elevated intracerebral glutamine synthesis play in this a facilitating role. The similarity in symptomatology of the clinical picture of HE and the serotonergic syndrome support this hypothesis. Due to contradictory research findings the role of the GABA-ergic system and the occurrence of HE remains unclear.

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Inhibition of endotoxin-induced pulmonary vasoconstriction in dogs by alpha-methyl dopa

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.6.987 ◽

1963 ◽

Vol 204 (6) ◽

pp. 987-990 ◽

Cited By ~ 8

Author(s):

J. Albrecht Koehler ◽

Theofilos J. Tsagaris ◽

Hiroshi Kuida ◽

Hans H. Hecht

Keyword(s):

Venous Hypertension ◽

Serotonin Synthesis ◽

Vascular Effects ◽

E Coli ◽

Group Of Seven ◽

Pulmonary Vasoconstriction ◽

Portal Venous Hypertension ◽

Physiologic Parameters ◽

Pulmonary Arterial ◽

Antihistaminic Drug

The demonstration in a previous study of the effectiveness of an antihistaminic drug in blocking some of the systemic but not the pulmonary vascular effects of endotoxin led to the study of the effect of an inhibitor of serotonin synthesis, alpha-methyl 3,4-dihydroxyphenylalanine (α-m dopa). One group of seven dogs was pretreated with a single dose of 250 mg, and a second group of six animals with three doses of 250 mg, each given at 10-min intervals. Results in these two groups were compared with those in six control animals. Purified E. coli endotoxin, 1 mg/kg, was administered intravenously in all 19 experiments. Intravenous administration of α-m dopa alone had no effect on measured physiologic parameters. Compared with the endotoxin response in control animals, pretreatment with either dose level appeared to have no effect on the magnitude or duration of systemic arterial hypotension, portal venous hypertension, or drop in cardiac output. However, pretreatment with 250-mg and 750-mg doses was associated with significant reduction and abolition, respectively, of pulmonary arterial hypertension. The results are consistent with the interpretation that the pulmonary vasoconstrictive response to endotoxin is mediated through the release of serotonin and that α-m dopa blocks this response by interfering with the synthesis of this intermediary.

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