Dopamine mediates a directionally opposite correlation between empathy and the reinforcing effects of amphetamine and gambling in people with gambling disorder vs. healthy controls

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2024-09-03 DOI:10.1016/j.pbb.2024.173865

Martin Zack , Arian Behzadi , Candice Biback , Bindiya Chugani , Dan DiGiacomo , Tim Fang , Sylvain Houle , Aditi Kalia , Daniela Lobo , Doris Payer , Constantine X. Poulos , Pablo M. Rusjan , Kelly Smart , Daniel Tatone , Jerry Warsh , Alan A. Wilson , James L. Kennedy

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Abstract

Understanding the relationship between empathy, subjective effects of addictive reinforcers and dopamine function in people with gambling disorder (PGD) vs. healthy controls (HCs) may inform GD treatment. The current investigation addressed this issue via retrospective analysis of data from three studies using amphetamine and a slot machine (SLOTS) as reinforcers in PGD and HCs. The Empathy scale of Eysenck's Impulsiveness Questionnaire assessed trait Empathy. The Gamblers Beliefs Questionnaire assessed cognitive distortions. The Eysenck Lie scale assessed socially desirable responding. PET scans quantified dopamine receptor expression and amphetamine-induced dopamine release in Study 1. Pre-treatment with the D2-receptor (D2R)-preferring antagonist, haloperidol or D1R-D2R antagonist, fluphenazine before SLOTS tested the role of D2 autoreceptors and post-synaptic D2R in Study 2. Pre-treatment with the multi-system indirect dopamine agonist, modafinil before SLOTS assessed the reliability of correlations in PGD. Striatal D2R expression predicted greater Empathy and lower amphetamine ‘Liking’ in HCs, and predicted greater symptom severity in PGD. Empathy predicted lower ‘Exciting’ effects of SLOTS under placebo in HCs; no correlation emerged under either antagonist. Relative to placebo, haloperidol decreased, whereas fluphenazine increased, the positive correlation between Empathy and Exciting effects of SLOTS in PGD. Modafinil markedly reduced the positive correlation between Empathy and Exciting effects of SLOTS seen under placebo in PGD. Empathy predicted greater cognitive distortions in PGD in all studies. Lie scale variance influenced several primary effects. Prior research linking the insula with Empathy, reactivity to interoceptive signals for risky rewards (uncertainty), and cognitive distortions, provides a parsimonious account for these results.

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与健康对照组相比，多巴胺在赌博障碍患者的移情与安非他明和赌博的强化效应之间起着方向相反的中介作用。

了解赌博障碍患者（PGD）与健康对照组（HCs）之间的共鸣、成瘾性强化物的主观效果和多巴胺功能之间的关系，可为赌博障碍的治疗提供参考。目前的调查通过回顾性分析三项研究的数据来解决这一问题，这三项研究使用安非他明和老虎机（SLOTS）作为强化剂，分别针对 PGD 和 HCs。艾森克冲动性问卷的移情量表评估了特质移情。赌徒信念问卷评估认知扭曲。艾森克谎言量表评估社会期望反应。在研究 1 中，PET 扫描量化了多巴胺受体的表达和苯丙胺诱导的多巴胺释放。在研究2中，用D2受体（D2R）优先拮抗剂氟哌啶醇或D1R-D2R拮抗剂氟奋乃静进行SLOTS前处理，测试D2自身受体和突触后D2R的作用。在进行 SLOTS 前使用多系统间接多巴胺激动剂莫达非尼评估了 PGD 中相关性的可靠性。纹状体 D2R 的表达预示着 HCs 中更大的移情作用和更低的苯丙胺 "喜欢"，并预示着 PGD 中更严重的症状。在安慰剂作用下，共情预示着高危人群中 SLOTS 的 "兴奋 "效应较低；在两种拮抗剂作用下均未出现相关性。与安慰剂相比，氟哌啶醇降低了PGD患者移情和SLOTS兴奋效应之间的正相关性，而氟奋乃静则提高了这一相关性。莫达非尼明显降低了在安慰剂作用下PGD患者移情和SLOTS兴奋效应之间的正相关性。在所有研究中，移情预示着 PGD 的认知扭曲程度更大。谎言量表差异影响了几种主要效应。之前的研究将脑岛与移情、对风险奖赏（不确定性）感知信号的反应性以及认知扭曲联系起来，为这些结果提供了一个合理的解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.