Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

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 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. 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.