Hutchison Kent E, Ray Lara, Sandman Erica, Rutter Marie-Christine, Peters Annie, Davidson Dena, Swift Robert
Department of Psychology, University of Colorado at Boulder, Boulder, CO 80309-0345, USA.
Neuropsychopharmacology. 2006 Jun;31(6):1310-7. doi: 10.1038/sj.npp.1300917.
Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol, that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of tandem repeats (VNTR) polymorphism, and that the effect of olanzapine (a D2/D4 antagonist) is more pronounced among individuals with this allele. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week, randomized, placebo-controlled trial among individuals with and without the seven-repeat allele. Participants who met DSM IV criteria for alcohol dependence were randomly assigned to receive olanzapine (5 mg) or a placebo over the course of the trial. After 2 weeks of treatment, participants completed a cue reactivity assessment. The results suggested that participants who were homozygous or heterozygous for the seven (or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial, whereas individuals with the shorter alleles did not respond favorably to olanzapine.
先前的研究表明，奥氮平可降低给予酒精启动剂量后的渴求感，在多巴胺D4受体基因（DRD4）可变数目串联重复序列（VNTR）多态性的七重复等位基因个体中，给予酒精启动剂量后的渴求感更强，且奥氮平（一种D2/D4拮抗剂）对具有该等位基因的个体的作用更为显著。本研究检验了以下假设：在一项为期12周的随机、安慰剂对照试验中，对于有或没有七重复等位基因的个体，奥氮平在减少线索诱发的渴求感方面可能具有不同的效果，并且作为酒精依赖的治疗方法也可能具有不同的效果。符合《精神疾病诊断与统计手册》第四版（DSM IV）酒精依赖标准的参与者在试验过程中被随机分配接受奥氮平（5毫克）或安慰剂。治疗2周后，参与者完成了线索反应性评估。结果表明，DRD4 VNTR七（或更长）重复等位基因的纯合子或杂合子参与者在12周试验过程中对奥氮平的反应是线索诱发的渴求感降低以及酒精摄入量减少，而等位基因较短的个体对奥氮平没有良好反应。
