title: The separate and combined effects of monoamine oxidase A inhibition and nicotine on the mismatch negativity event related potential.
abstract: The mismatch negativity (MMN) auditory event-related potential (ERP) has been extensively studied as a potential biomarker for abnormal auditory processing in schizophrenia (SZ), a population which exhibits abnormally high smoking rates. The relationship between nicotinic activation and cognition in SZ may be related to underlying nicotinic and NMDA receptor dysfunction within the disease. However, transient cognitive improvements via smoking in patients may also result from monoamine oxidase (MAO) inhibition, achieved through tobacco smoke. In 24 healthy non-smoking males, we investigated the separate and combined effects of nicotine and MAO-A inhibition via moclobemide (75mg) on the optimal-5 variation of the MMN paradigm. No significant drug effects were observed in our total sample, however, stratification of individuals into low (N=12) and high (N=12) baseline MMN amplitude groups revealed increases in duration MMN amplitude relative to placebo by nicotine, as well as moclobemide, but not after the combination of the two. Because previous research has shown there was no effect of monoamine modulation on MMN, this study shows an unexpected effect of moclobemide on duration MMN.
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: dylan.m.smith@gmail.com.
authors.forename: Dylan M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: Department of Psychology, Mount Saint Vincent University, Halifax, Nova Scotia, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Fisher
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
authors.affiliation: Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada.
authors.forename: Vadim
authors.initials: V
authors.lastname: Ilivitsky
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada.
authors.forename: Verner
authors.initials: V
authors.lastname: Knott
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D020912:Moclobemide / Q000008:administration & dosage*; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D009538:Nicotine / Q000008:administration & dosage*; D010775:Photic Stimulation / Q000379:methods
chemical_list: D004338:Drug Combinations; D008996:Monoamine Oxidase Inhibitors; D009538:Nicotine; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D020912:Moclobemide
keywords: MAO inhibition; Mismatch negativity; Moclobemide; Nicotine; Schizophrenia