OPRM1 gene variants modulate amphetamine-induced euphoria in humans.
OPRM1 gene variants modulate amphetamine-induced euphoria in humans.
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DOI：
10.1111/j.1601-183x.2010.00655.x
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发表时间：
2011-03
期刊：
影响因子：
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通讯作者：
de Wit H
中科院分区：
文献类型：
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作者：
Dlugos AM;Hamidovic A;Hodgkinson C;Shen PH;Goldman D;Palmer AA;de Wit H
μ阿片受体不仅参与了吗啡等阿片类药物的奖赏效应，也参与了安非他明等精神刺激剂的奖赏效应。本研究旨在研究安非他明的主观反应与μ阿片受体基因多态和单倍型的关系，包括外显子突变体rs1799971(Asp40Asn)。162名高加索志愿者参加了三个疗程，分别服用安慰剂或d-苯丙胺(10毫克和20毫克)。研究了摄入d-苯丙胺后自我报告的快感、能量和刺激(ARCI-49)水平与OPRM1基因多态性之间的关系。内含子SNPs rs510769和rs2281617与安非他明10 mg后的欣快感、活力和刺激感显著相关。快感、能量和刺激的感觉也与rs1799971和rs510769形成的2-SNP单倍型和rs1918760、rs2281617和rs1998220形成的3-SNP单倍型有关。这些结果支持这样的假设，即μ阿片受体基因的遗传变异性影响安非他明的主观效应，并可能为预防和治疗精神刺激剂滥用提供新的策略。
The μ-opioid receptor is involved in the rewarding effects of not only opioids like morphine but also psychostimulants like amphetamine. This study aimed to investigate associations between subjective response to amphetamine and genetic polymorphisms and haplotypes in the μ-opioid receptor including the exonic variant rs1799971 (Asp40Asn). 162 Caucasian volunteers participated in three sessions receiving either placebo or d-amphetamine (10 and 20 mg). Associations between levels of self-reported Euphoria, Energy and Stimulation (ARCI-49) after d-amphetamine ingestion and polymorphisms in OPRM1 were investigated. The intronic SNPs rs510769 and rs2281617 were associated with significantly higher ratings of Euphoria, Energy and Stimulation after 10 mg amphetamine. Feelings of Euphoria, Energy and Stimulation were also found to be associated with a 2-SNP haplotype formed with rs1799971 and rs510769 and a 3-SNP haplotype formed with rs1918760, rs2281617 and rs1998220. These results support the hypothesis that genetic variability in the μ-opioid receptor gene influences the subjective effects of amphetamine and may suggest new strategies for prevention and treatment of psychostimulant abuse.