title: Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms.
abstract: BACKGROUND
  Pharmacological and genetic modulation of cholinergic nicotinic neurotransmission influence visuospatial attention in humans. Prior studies show that nicotine as well as a single nucleotide polymorphism (SNP) in the gene coding for the alpha 4 subunit of the nicotinic acetylcholine receptor (CHRNA4) modulate visuospatial attention and distractor interference. The CHRNA4 gene synergistically interacts with a polymorphism in the dopaminergic receptor type d2 (DRD2) gene and impacts brain structure and cognition.
  
  
  OBJECTIVE
  We aimed to investigate whether CHRNA4 and DRD2 genotypes alter the effects of nicotine on distractor interference.
  
  
  METHODS
  Fifty-eight young healthy non-smokers were genotyped for CHRNA4 (rs1044396) and DRD2 (rs6277). They received either 7 mg transdermal nicotine or a matched placebo in a double-blind, within-subject design 1 h prior to performing a visual search task with distractors.
  
  
  RESULTS
  In isolation, DRD2 but not CHRNA4 genotype modulated the effects of nicotine on distractor interference with DRD2 CC carriers showing the strongest reduction of distractor interference after nicotine administration. A further analysis provided additional evidence that this effect was driven by those subjects, who carried at least one C allele in the CHRNA4 gene.
  
  
  CONCLUSIONS
  The effects of nicotine on distractor interference are modulated synergistically by cholinergic and dopaminergic genetic variations. Hence, both genes may contribute to the often reported individual variability in cognitive and neural effects of nicotine.
authors: Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111, Oldenburg, Germany. st.ahrens@uni-oldenburg.de.
authors: Stefan
authors: S
authors: Ahrens
authors: Department of Psychology, University of Bonn, Bonn, Germany.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
authors: Sebastian
authors: S
authors: Markett
authors: Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111, Oldenburg, Germany.
authors: Thomas P K
authors: TP
authors: Breckel
authors: Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111, Oldenburg, Germany.|Medical Physics, Department of Medical Physics and Acoustic, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany.
authors: Oliver
authors: O
authors: Behler
authors: Department of Psychology, University of Bonn, Bonn, Germany.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
authors: Martin
authors: M
authors: Reuter
authors: Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111, Oldenburg, Germany.|Cluster of Excellence "Hearing4all", Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.|Research Center Neurosensory Science, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany.
authors: Christiane M
authors: CM
authors: Thiel
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D010775:Photic Stimulation / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D055815:Young Adult
chemical_list: D009538:Nicotine; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic
keywords: Acetylcholine; Distraction; Dopamine; Flexibility; Genetics; Nicotine; Pharmacology; SNP; Selective attention
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