Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Department for Social and Preventive Medicine, University of Potsdam, Potsdam, Germany.
J Psychopharmacol. 2021 May;35(5):566-578. doi: 10.1177/0269881121991992. Epub 2021 Mar 16.
Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian-instrumental interactions. The A118G polymorphism of the gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the polymorphism is associated with the PIT effect and relapse in AD.
Using a PIT task, we examined three independent samples: young healthy subjects ( = 161), detoxified alcohol-dependent patients ( = 186) and age-matched healthy controls ( = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the gene. Relapse was assessed after three months.
In all three samples, participants with the minor G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse.
These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.
条件性线索-操作性条件反射关联转移（PIT）可量化刺激与奖惩关联后改变操作性行为的程度。在酒精依赖（AD）中，PIT 效应是线索诱发复饮的典型模型。临床前研究表明，阿片系统在调节条件性线索与操作性条件反射之间的相互作用中起着关键作用。 基因的 A118G 多态性影响阿片受体的可用性和功能。此外，该多态性与线索诱导的趋近行为相互作用，是 AD 药物治疗反应的潜在生物标志物。在这项研究中，我们测试了 基因的 A118G 多态性是否与 AD 中的 PIT 效应和复饮有关。
我们使用 PIT 任务检查了三个独立的样本：年轻健康受试者（n=161）、脱毒酒精依赖患者（n=186）和年龄匹配的健康对照组（n=105）。我们使用了一项旨在评估学习机制在 AD 发生和维持中的作用的更大研究的数据。对受试者进行了 基因的 A118G（rs1799971）多态性的基因分型。在三个月后评估复饮情况。
在所有三个样本中，携带较小的 基因 G-等位基因（G+携带者）的参与者在没有学习差异的情况下表现出 PIT 效应的表达增加。复饮与 基因多态性无关。相反，PIT 效应增加的 G+携带者尤其容易复饮。
这些结果支持阿片系统在激励性激励中的作用。此外，它们提供了异常激励加工的机制模型，并与阿片受体靶点在 AD 治疗中的药理学潜力一致。
