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Dietary manipulation of serotonergic and dopaminergic function in C57BL/6J mice with amino acid depletion mixtures

Abstract

Amino acid (AA) depletion techniques have been used to decrease serotonin (5-HT) and/or dopamine (DA) synthesis after administration of a tryptophan (acute tryptophan depletion, ATD) or phenylalanine/tyrosine-free (phenylalanine–tyrosine depletion, PTD) AA formula and are useful as neurochemical challenge procedures to study the impact of DA and 5-HT in patients with neuropsychiatric disorders. We recently demonstrated that the refined Moja-De ATD paradigm decreases brain 5-HT synthesis in humans and mice and lowers brain 5-HT turnover. In the present study we validated the neurochemical effects of three developed AA formulas on brain 5-HT and DA function in mice. To distinguish the direct and indirect effects of such mixtures on 5-HT and DA and to determine whether additive depletion of both could be obtained simultaneously, we compared the effects of ATD for 5-HT, PTD for DA, and a combined monoamine depletion mixture (CMD) compared to a control condition consisting of a balanced amino acid mixture. Food-deprived male C57BL/6J mice were gavaged with AA mixtures. Serum and brain samples were collected and analyzed for determination of tryptophan (Trp), tyrosine (Tyr), 5-HT, 5-HIAA, DA, DOPAC and HVA levels. ATD was the most effective at decreasing Trp, 5-HT and 5-HIAA. In contrast, PTD reduced Tyr globally but HVA only in certain brain regions. Although CMD affected both 5-HT and DA synthesis, it was less effective when compared with ATD or PTD alone. The present results demonstrate that two newly developed PTD and CMD formulas differentially impact brain 5-HT and DA synthesis relative to 5-HT-specific ATD Moja-De. Different effects on 5-HT and DA function by these mixtures suggest that the exact composition may be a critical determinant for effectiveness with respect to the administered challenge procedure.

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Acknowledgments

This study received funding from the Bundesministerium für Wirtschaft und Technologie (BMWi).

Conflict of interest

FDZ was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE) and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the German Society for Social Pediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation, the IZKF fund of the University Hospital of RWTH Aachen University, and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support and speaker honoraria by Shire Pharmaceuticals, Germany. In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship), and editorial fees from Co-Action Publishing (Sweden). All authors report no conflict of interest.

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Correspondence to Cristina L. Sánchez.

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Sánchez, C.L., Van Swearingen, A.E.D., Arrant, A.E. et al. Dietary manipulation of serotonergic and dopaminergic function in C57BL/6J mice with amino acid depletion mixtures. J Neural Transm 121, 153–162 (2014). https://doi.org/10.1007/s00702-013-1083-0

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  • DOI: https://doi.org/10.1007/s00702-013-1083-0

Keywords

  • Mice
  • Depletion
  • Serotonin
  • Dopamine
  • Combined monoamine depletion