Comings D E, Dietz G, Johnson J P, MacMurray J P
Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010, USA.
Neuroreport. 1999 Aug 2;10(11):2283-5. doi: 10.1097/00001756-199908020-00011.
Low amplitude of the P300 evoked potential waves has been linked to substance abuse. Defects in opioidergic genes regulating reward pathways have been implicated as risk factors in substance abuse. Since the rate of degradation of enkephalins regulates their CNS level, we focused on the MME gene for metallo-membrane endopeptidase (neutral endopeptidase, enkephalinase). We identified a GT repeat polymorphism 5' to the gene and examined its potential association with P300 wave amplitude in 25 male subjects with substance abuse. There was significant association of low mol. wt alleles with low amplitude of the P300 wave at the parietal (p = 0.0087) and coronal (p = 0.009) leads. These results support a role of endogenous opioids in the regulation of P300 wave amplitude.
P300诱发电位波幅降低与药物滥用有关。调节奖赏通路的阿片肽能基因缺陷被认为是药物滥用的危险因素。由于脑啡肽的降解速率调节其在中枢神经系统中的水平，我们重点研究了金属膜内肽酶（中性内肽酶，脑啡肽酶）的MME基因。我们在该基因5'端鉴定出一个GT重复多态性，并在25名药物滥用男性受试者中检测了其与P300波幅的潜在关联。低分子量等位基因与顶叶（p = 0.0087）和冠状（p = 0.009）导联处P300波的低波幅存在显著关联。这些结果支持内源性阿片类物质在调节P300波幅中发挥作用。
