THE MODERATING ROLE OF THE DOPAMINE TRANSPORTER 1 GENE ON P50 SENSORY GATING AND ITS MODULATION BY NICOTINE

被引:22
作者
Millar, A. [2 ]
Smith, D. [1 ,2 ]
Choueiry, J. [1 ]
Fisher, D. [3 ,4 ]
Albert, P. [2 ]
Knott, V. [1 ,2 ,3 ,4 ]
机构
[1] Univ Ottawa, Mental Hlth Res Inst, Royal Ottawa Mental Hlth Ctr, Ottawa, ON K1Z 7K4, Canada
[2] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1S 5B6, Canada
[3] Carleton Univ, Dept Psychol, Ottawa, ON K1S 5B6, Canada
[4] Carleton Univ, Inst Neurosci, Ottawa, ON K1S 5B6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
schizophrenia; P50; gating; dopamine transporter gene; nicotine; smoking; AUDITORY P50; SCHIZOTYPAL PERSONALITY; EVOKED-POTENTIALS; COMPUTER-MODEL; CA3; REGION; SCHIZOPHRENIA; INHIBITION; PREDICTS; GENOTYPE; SMOKING;
D O I
10.1016/j.neuroscience.2011.02.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:148 / 156
页数:9
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