Stefan Ahrens1, Sebastian Markett2,3, Thomas P K Breckel4, Oliver Behler4,5, Martin Reuter2,3, Christiane M Thiel4,6,7. 1. 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. 2. Department of Psychology, University of Bonn, Bonn, Germany. 3. Center for Economics and Neuroscience, University of Bonn, Bonn, Germany. 4. Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111, Oldenburg, Germany. 5. Medical Physics, Department of Medical Physics and Acoustic, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany. 6. Cluster of Excellence "Hearing4all", Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany. 7. Research Center Neurosensory Science, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany.
Abstract
RATIONALE: 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. CONCLUSION: 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.
RCT Entities:
RATIONALE: 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. CONCLUSION: 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.
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