Abstract
Video presentation of the entire lecture can be accessed here Background : Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT) synthesis. Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the bloodbrain 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. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols, possibly because of an administration in accordance with the body weight of the subjects. It has been used in the preliminary clinical studies, but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. Design : We tested ATD Moja-De (TRP-) in two strains of mice, C57BL/6 and BALB/cJ, which are reported to have impaired 5-HT synthesis relative to other strains of mice. Results : ATD Moja-De lowered brain TRP, significantly decreased central nervous 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 C57 BL/6 than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A tryptophan-balanced control mixture did not increase 5-HT or 5-HIAA. Conclusion : The present findings suggest that ATD Moja-De effectively suppresses central serotonergic function, and that the effects of ATD Moja-De are specific to serotonin function. (Published: 9 September 2013) Citation: Translational Developmental Psychiatry 2013, 1 : 18747 - http://dx.doi.org/10.3402/tdp.v1i0.18747
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]
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