RATIONALE: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence. OBJECTIVES: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory. MATERIALS AND METHODS: Working memory and brain function were assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes), each of whom was studied twice, once after placement of aplacebo patch and once after placement of a nicotine patch. Brain function was assessed using functional magnetic resonance imaging while the subjects performed a verbal working memory task. RESULTS: During performance of a task with high verbal working memory load, nicotine administration worsened performance accuracy and reduced the processing efficiency of brain regions that support phonological rehearsal during verbal working memory in carriers of the 957T allele. CONCLUSIONS: These findings are consistent with the notion that genetic variation in DRD2 contributes to individual variation in a range of behavioral and brain responses to nicotine in humans.
RCT Entities:
RATIONALE: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence. OBJECTIVES: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory. MATERIALS AND METHODS:Working memory and brain function were assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes), each of whom was studied twice, once after placement of a placebo patch and once after placement of a nicotine patch. Brain function was assessed using functional magnetic resonance imaging while the subjects performed a verbal working memory task. RESULTS: During performance of a task with high verbal working memory load, nicotine administration worsened performance accuracy and reduced the processing efficiency of brain regions that support phonological rehearsal during verbal working memory in carriers of the 957T allele. CONCLUSIONS: These findings are consistent with the notion that genetic variation in DRD2 contributes to individual variation in a range of behavioral and brain responses to nicotine in humans.
Authors: G E Swan; A M Valdes; H Z Ring; T V Khroyan; L M Jack; C C Ton; S J Curry; T McAfee Journal: Pharmacogenomics J Date: 2005 Impact factor: 3.550
Authors: Venkata S Mattay; Terry E Goldberg; Francesco Fera; Ahmad R Hariri; Alessandro Tessitore; Michael F Egan; Bhaskar Kolachana; Joseph H Callicott; Daniel R Weinberger Journal: Proc Natl Acad Sci U S A Date: 2003-04-25 Impact factor: 11.205
Authors: Matthew T Sutherland; Thomas J Ross; Diaá M Shakleya; Marilyn A Huestis; Elliot A Stein Journal: Psychopharmacology (Berl) Date: 2010-09-23 Impact factor: 4.530
Authors: Leslie K Jacobsen; Marina R Picciotto; Christopher J Heath; W Einar Mencl; Joel Gelernter Journal: Biol Psychiatry Date: 2008-12-05 Impact factor: 13.382
Authors: Stefan Ahrens; Sebastian Markett; Thomas P K Breckel; Oliver Behler; Martin Reuter; Christiane M Thiel Journal: Psychopharmacology (Berl) Date: 2015-02-03 Impact factor: 4.530
Authors: Riju Ray; James Loughead; Ze Wang; John Detre; Edward Yang; Ruben Gur; Caryn Lerman Journal: Behav Brain Res Date: 2008-06-05 Impact factor: 3.332