Abstract
Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP−) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain- specific effect of ATD Moja-De on anxiety-like behavior.
Highlights
The neurotransmitter serotonin (5-HT) plays a key role in many physiological processes, including cognition and mood, which are typically affected in clinical depression and anxiety disorder
The main finding of this study is that the treatment with acute tryptophan depletion (ATD) Moja-De (TRP2) decreased brain TRP and subsequently brain 5HT synthesis as shown by 5-HTP after decarboxylase inhibition and by decreases in 5-HT and 5-HIAA levels of both strains of mice relative to TRP+
The ability of ATD to decrease 5-HT synthesis and content is well established in rats and in humans [1,2,8], one report in mice yielded equivocal results [23]
Summary
The neurotransmitter serotonin (5-HT) plays a key role in many physiological processes, including cognition and mood, which are typically affected in clinical depression and anxiety disorder. A well-established method to study the effects of 5-HT in the human brain is to lower the central nervous 5-HT synthesis rate by diminishing the availability of tryptophan (TRP), the amino acid precursor of 5-HT. This technique is called acute tryptophan depletion (ATD). The rate controlling step in central nervous 5HT synthesis is the conversion of TRP into L-5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase (TPH) [1]. As TPH is not saturated at physiological concentrations of TRP, diminished substrate availability for TPH decreases brain 5-HT synthesis and release [1]. Ingestion of a TRP-free amino acid mixture provides a dose of large neutral amino acids which compete with endogenous TRP for transport across the blood-brain barrier, and subsequently lowers brain TRP levels, 5-HT synthesis and levels of 5-HIAA, the primary metabolite of 5-HT [4,5,6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
