The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride
The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride
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DOI：
10.1111/add.12066
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发表时间：
2013-05-01
期刊：
影响因子：
6
通讯作者：
Zack, Martin
中科院分区：
文献类型：
--
作者：
Boileau, Isabelle;Payer, Doris;Zack, Martin
目的病理性赌博（PG）与物质使用障碍（SUD）具有相同的诊断特征，但PG的神经化学机制尚不清楚。由于多巴胺（DA），一种参与奖励和强化的神经递质，可能参与其中，我们使用正电子发射断层扫描（PET）来测试PG是否与D2和D3受体水平异常有关，正如在SUD中观察到的那样。设计比较PG和健康对照（HC）受试者的病例对照研究。设置学术研究影像中心。参与者13名非寻求治疗的男性符合DSM-IV PG标准，12名匹配HC（其中11名完成PET）。两次PET扫描(一次使用D3受体偏好激动剂[11C]-（+)-丙基-六氢萘-恶嗪（PHNO），另一次使用[11C]raclopride）来评估D2/3 DA受体的可用性，以及行为测量（自我报告问卷和老虎机游戏）来评估主观影响及其与PET测量的关系。两种放射性示踪剂在纹状体和黑质（SN）的结合在两组之间没有差异（均为0.1）。在PG中，SN中的[11C]-(+)- phno结合与赌博严重程度（r=0.57， P=0.04）和冲动性（r=0.65， P=0.03）相关，其中信号主要归因于D3受体。在HC中，[11C]背纹状体的raclopride结合与赌博的主观效应（r=0.70， P=0.03）和冲动（r=0.70， P=0.03）呈负相关。与物质使用障碍不同，健康受试者和病态赌徒之间的D2/D3水平似乎没有显著差异，这表明低受体可用性可能不是成瘾的必要特征。然而，[11C]-(+)- phno结合与赌博严重程度/冲动之间的关系表明D3受体参与冲动/强迫行为。
Aims Pathological gambling (PG) shares diagnostic features with substance use disorder (SUD), but the neurochemical mechanisms underlying PG are poorly understood. Because dopamine (DA), a neurotransmitter implicated in reward and reinforcement, is probably involved, we used positron emission tomography (PET) to test whether PG is associated with abnormalities in D2 and D3 receptor levels, as observed in SUD. Design Casecontrol study comparing PG to healthy control (HC) subjects. Setting Academic research imaging centre. Participants Thirteen non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11 of whom completed PET). Measurements Two PET scans (one with the D3 receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other with [11C]raclopride) to assess D2/3 DA receptor availability, and behavioural measures (self-report questionnaires and slot-machine game) to assess subjective effects and relationships to PET measures. Findings Binding of both radiotracers did not differ between groups in striatum or substantia nigra (SN) (all 0.1). Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable primarily to D3 receptors, correlated with gambling severity (r=0.57, P=0.04) and impulsiveness (r=0.65, P=0.03). In HC, [11C]raclopride binding in dorsal striatum correlated inversely with subjective effects of gambling (r=0.70, P=0.03) and impulsiveness (r=0.70, P=0.03). Conclusions Unlike with substance use disorder, there appear to be no marked differences in D2/D3 levels between healthy subjects and pathological gamblers, suggesting that low receptor availability may not be a necessary feature of addiction. However, relationships between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests involvement of the D3 receptor in impulsive/compulsive behaviours.