Acute dopamine and/or serotonin depletion does not modulate mismatch negativity (MMN) in healthy human participants.

Rationale: Schizophrenia is commonly associated with impairments in pre-attentive change detection, as represented by reduced mismatch negativity (MMN). While the neurochemical basis of MMN has been linked to N-methyl-D: -aspartic acid (NMDA) receptor function, the roles of the dopaminergic and/or the serotonergic systems are not fully explored in humans.

Objectives: The aim of the present study was to investigate the effects of acutely depleting dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) alone or simultaneously by depleting their amino acid precursors on MMN in healthy participants.

Methods: Sixteen healthy male subjects participated in a double-blind, placebo-controlled, cross-over design in which each subject's duration MMN was assessed under four acute treatment conditions separated by a 5-day washout period: balanced amino acid control (no depletion), tyrosine/phenylalanine depletion (to reduce DA neurotransmission), tryptophan depletion (to reduce 5-HT neurotransmission) and tryptophan/tyrosine/phenylalanine depletion (to reduce DA and 5-HT neurotransmission simultaneously).

Results: Acute depletion of either DA and 5-HT alone or simultaneously had no effect on MMN.

Conclusions: These findings suggest that modulation of the dopaminergic and serotonergic systems acutely does not lead to changes in MMN.