Norepinephrine transporter gene variation modulates acute response to D-amphetamine
Norepinephrine transporter gene variation modulates acute response to D-amphetamine
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DOI：
10.1016/j.biopsych.2006.09.031
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发表时间：
2007-06-01
影响因子：
10.6
通讯作者：
de Wit, Harriet
中科院分区：
文献类型：
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作者：
Dlugos, Andrea;Freitag, Christine;de Wit, Harriet
背景资料：对兴奋剂药物（如安非他明）的主观反应的个体差异可能会影响滥用风险以及对这些药物的临床治疗反应。由于苯丙胺的影响是介导的部分由去甲肾上腺素转运体（SLC 6A 2），我们研究了情绪反应苯丙胺SLC 6A 2基因polymorphisms.Methods：99名健康志愿者参加了三个会议，他们随机接受安慰剂或D-苯丙胺（10毫克或20毫克）在双盲条件下的个体间差异。所有受试者均完成主观效应的自评量表（心境状态量表）。之后，所有的人都进行了8个SLC 6A 2基因多态性的基因分型。个体基因型和单倍型进行了investigated.Results：内含子36001 C/C（rs 47958）基因型与增加积极情绪和抑郁后20毫克的D-苯丙胺。积极的情绪和情绪水平也被发现与单倍型GCC相关，GCC由28257 G/C（rs36017），28323 C/T（rs 2270935）和36001 A/C（rs 47958）形成。这些发现仍然显着调整后，多重testing.Conclusions：SLC 6A 2基因的多态性与D-苯丙胺的情绪反应。如果得到证实，这一观察结果可能有助于更好地理解个体间对安非他明的临床反应和安非他明成瘾风险的差异。
Background: Individual differences in subjective responses to stimulant drugs such as amphetamine may influence risk of abuse as well as clinical-treatment response to these drugs. Because the effects of amphetamine are mediated in part by the norepinephrine transporter (SLC6A2), we examined interindividual differences in mood response to amphetamine in relation to SLC6A2 gene polymorphisms.Methods: Ninety-nine healthy volunteers participated in three sessions in which they randomly received either placebo or D-amphetamine (10 mg or 20 mg) under double-blind conditions. Every subject completed self-report measures on subjective effects (Profile of Mood States). Afterward, all individuals were genotyped for eight SLC6A2 gene polymorphisms. Individual genotypes and haplotypes were investigated.Results: The intronic 36001C/C (rs47958) genotype was associated with increases in positive mood and elation after 20 Mg of D-amphetamine. Positive mood and elation levels were also found to be associated with the haplotype GCC formed from 28257G/C (rs36017),28323C/T (rs2270935), and 36001 A/C (rs47958). These findings remained significant after adjustment for multiple testing.Conclusions: Polymorphisms in the SLC6A2 gene were associated with mood responses to D-amphetamine. If confirmed, this observation may contribute to abetter understanding of interindividual variations in the clinical response to amphetamine and in the risk of becoming addicted to amphetamine.