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

Author(s): Leung S, Croft RJ, Guille V, Scholes K, O'Neill BV, Phan KL, Nathan PJ

Affiliation(s): Brain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology, P.O. Box 218, John Street Hawthorn, 3122, Melbourne, VIC, Australia. smleung@groupwise.swin.edu.au

Publication date & source: 2010-02, Psychopharmacology (Berl)., 208(2):233-44. Epub 2009 Dec 10.

Publication type: Comparative Study; Randomized Controlled Trial

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.

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