Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice.
BACKGROUND
Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT) or dopamine (DA) in the central nervous system. The availability of these substances within the brain is determined by the blood-brain barrier (BBB) that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP) compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis.


OBJECTIVE
The present study compared the effects of a simplified acute tryptophan depletion (SATD) mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De) and its TRP-balanced control (BAL).


METHODS
The SATD formula is composed of only three large neutral AAs: phenylalanine (PHE), leucine (LEU), and isoleucine (ILE). BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens).


RESULTS
Both ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration.


CONCLUSIONS
A simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders.
Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JARA Brain, RWTH Aachen University, Aachen, Germany.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Cristina L
CL
Sánchez
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Amanda E D
AE
Van Swearingen
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Andrew E
AE
Arrant
Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JARA Brain, RWTH Aachen University, Aachen, Germany.
Caroline S
CS
Biskup
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Cynthia M
CM
Kuhn
Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JARA Brain, RWTH Aachen University, Aachen, Germany.|Department of Child and Adolescent Psychiatry, School of Paediatrics and Child Health & School of Psychiatry and Clinical Neurosciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA, Australia.|Specialised Child and Adolescent Mental Health Services (CAHMS), Department of Health, Perth, WA, Australia; florian.zepf@uwa.edu.au.
Florian D
FD
Zepf
acute tryptophan depletion; amino acid; dopamine; formulation; mice; serotonin