title: The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine.
abstract: Although schizophrenia has been considered primarily a disease of dopaminergic neurotransmission, the role of dopamine in auditory sensory gating deficits in this disorder and their amelioration by smoking/nicotine is unclear. Hypothesizing that individual differences in striatal dopamine levels may moderate auditory gating and its modulation by nicotine, this preliminary study used the mid-latency (P50) auditory event-related potential (ERP) to examine the single dose (6 mg) effects of nicotine (vs. placebo) gum on sensory gating in 24 healthy nonsmokers varying in the genetic expression of the dopamine transporter (DAT). Consistent with an inverted-U relationship between dopamine level and the drug effects, individuals carrying the 9R (lower gene expression) allele, which is related to greater striatal dopamine levels, tended to evidence increased baseline gating compared to 10R (higher gene expression) allele carriers and showed a reduction in gating with acute nicotine. The present results may help to understand the link between excessive smoking and sensory gating deficits in schizophrenia and to explain the potential functional implications of genetic disposition on nicotinic treatment in schizophrenia.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1S5B6, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Millar
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Choueiry
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: P
authors.initials: P
authors.lastname: Albert
authors.forename: V
authors.initials: V
authors.lastname: Knott
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects* / Q000235:genetics*; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018722:Nicotinic Agonists; D009538:Nicotine; D004298:Dopamine