کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4337953 1614835 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Effects of COMT genotype on sensory gating and its modulation by nicotine: Differences in low and high P50 suppressors
چکیده انگلیسی


• Low Val/Val genotype exhibited the poorest P50 sensory gating at baseline.
• Nicotine benefitted gating in low suppressors and impaired gating in high suppressors.
• Improvement with nicotine was most evident in Val carriers who were low suppressors.
• Impairment with nicotine was most evident in Met carriers who were high suppressors.

Elevated smoking rates seen in schizophrenia populations may be an attempt to correct neuropathologies associated with deficient nicotinic acetylcholine receptors and/or dopaminergic systems using exogenous nicotine. However, nicotine’s effects on cognitive processing and sensory gating have been shown to be baseline-dependent. Evidence of a restorative effect on sensory gating deficits by nicotine-like agonists has been demonstrated, however, its underlying mechanisms in the context of dopamine dysregulation are unclear. Catechol-O-methyltransferase (COMT), a key dopamine regulator in the brain, contains a co-dominant allele in which a valine-to-methionine substitution causes variations in enzymatic activity leading to reduced synaptic dopamine levels in the Val/Val genotype. Using a randomized, double-blind, placebo-controlled design with 57 non-smokers, this study examined the effects of COMT genotype on sensory gating and its modulation by nicotine in low vs. high suppressors. The results were consistent with the hypothesis that increased dopamine resulting from nicotine stimulation or Met allelic activity would benefit gating in low suppressors and impair gating in high suppressors, and that this gating improvement with nicotine would be more evident in Val carriers who were low suppressors, while the gating impairment would be more evident in Met carriers who were high suppressors. These findings reaffirm the importance of baseline-dependency and suggest a subtle relationship between COMT genotype and baseline-stratified levels of sensory gating, which may help to explain the variability of cognitive abilities in schizophrenia populations.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 241, 25 June 2013, Pages 147–156
نویسندگان
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