[Genetic vulnerability of methamphetamine dependence].

Yuki Moriya, Yoshiyuki Kasahara, Ichiro Sora
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Abstract

Methamphetamine (METH) dependence show strong familial and genetic influences in family and twin studies. METH exerts its reinforcing effects by modulating monoaminergic transmission, of which dopamine is supposed to be important. Previously, experimental animals were being used to identify mechanisms of action of METH that are related to its abuse and toxicity, and genetic mouse models have also been used to define genes that may predict risk for the development of drug addiction. We found that genetic variances of dopamine transporter, dopamine receptor, micro-opioid receptor, serotonin 1A receptor, serotonin 6 receptor, and adenosine 2A adenosine receptor could be vulnerability factors for METH dependence or psychosis in the Japanese population. Genetic analysis with a genome-wide association study (GWAS)-based approach has been successful for investigating the genetic influences of METH dependence and other complex features. Collaborative studies with JGIDA and NIDA/NIH have obtained the results that the genetic vulnerability to METH dependence contributes to other major drug addiction. The genetic studies for METH dependence might help to identify the risk of individuals and to develop treatments that take advantage of individual genetic information in the future.

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[甲基苯丙胺依赖的遗传脆弱性]。
甲基苯丙胺(冰毒)依赖在家庭和双胞胎研究中显示出强烈的家族和遗传影响。甲基苯丙胺通过调节单胺能传递发挥强化作用,其中多巴胺被认为是重要的。以前,实验动物被用来确定甲基苯丙胺的作用机制,这些机制与它的滥用和毒性有关,遗传小鼠模型也被用来确定可能预测药物成瘾风险的基因。我们发现,多巴胺转运体、多巴胺受体、微阿片受体、5 -羟色胺1A受体、5 -羟色胺6受体和腺苷2A腺苷受体的遗传变异可能是日本人群甲基苯丙胺依赖或精神病的易感因素。基于全基因组关联研究(GWAS)的遗传分析方法已经成功地研究了甲基安非他明依赖和其他复杂特征的遗传影响。与JGIDA和NIDA/NIH的合作研究已经获得了甲基安非他明依赖的遗传易感性有助于其他主要药物成瘾的结果。对冰毒依赖的基因研究可能有助于确定个体的风险,并在未来开发出利用个体遗传信息的治疗方法。
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Experience-dependent development of visual cortical functions. Experimental disease models for mechanistic understanding and drug discovery for psychiatric disorders. [Basal Ganglia Circuit Mechanisms in Cognitive Learning]. The contribution of neuroplasticity induced in cholinergic neurons of the laterodorsal tegmental nucleus to cocaine addiction. [Neuroimaging studies of depression: Current status and future direction.]
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