Original Investigation

Psychopharmacology

, Volume 208, Issue 2, pp 233-244

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

  • Sumie LeungAffiliated withBrain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology Email author 
  • , Rodney J. CroftAffiliated withBrain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of TechnologyDepartment of Psychology, Faculty of Health and Behavioural Sciences, University of Wollongong
  • , Valérie GuilleAffiliated withBrain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology
  • , Kirsty ScholesAffiliated withBrain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology
  • , Barry V. O’NeillAffiliated withBrain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology
  • , K. Luan PhanAffiliated withDepartment of Psychiatry, University of Michigan
  • , Pradeep J. NathanAffiliated withBrain Mapping Unit, Department of Psychiatry, University of CambridgeSchool of Psychology, Psychiatry and Psychological Medicine, Monash UniversityClinical Unit Cambridge, GlaxoSmithKline Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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.

Keywords

Mismatch negativity MMN Dopamine Serotonin Schizophrenia Cognition Tryptophan depletion Tyrosine depletion Monoamine Change detection