Dietary manipulation of serotonergic and dopaminergic function in C57BL/6J mice with amino acid depletion mixtures.
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.
Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Neuenhofer Weg 21, 52074, Aachen, Nordrhein-Westfalen, Germany, csanchez@ukaachen.de.
Cristina L
CL
Sánchez
Amanda E D
AE
Van Swearingen
Andrew E
AE
Arrant
Cynthia M
CM
Kuhn
Florian D
FD
Zepf
D015102:3,4-Dihydroxyphenylacetic Acid; D000596:Amino Acids; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D005526:Food, Formulated; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010649:Phenylalanine / Q000172:deficiency; D012701:Serotonin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000172:deficiency; D014443:Tyrosine / Q000172:deficiency
D000596:Amino Acids; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D014443:Tyrosine; D010649:Phenylalanine; D014364:Tryptophan; D004298:Dopamine; D006719:Homovanillic Acid