1 Molecular Brain Sciences Research Department, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
2 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
J Psychopharmacol. 2019 Aug;33(8):1015-1029. doi: 10.1177/0269881119855972. Epub 2019 Jun 20.
The functional role of dopamine D1 and D2 receptors in gambling disorder (GD) remains unclear.
This study aimed to investigate the role of D1 activation and the moderating effects of impulsivity, a trait linked with weaker D2-mediated inhibition of dopamine release, in GD subjects.
Thirty (nine female) non-comorbid GD subjects with low (LI), moderate (MI), or high impulsivity (HI) received the preferential D2 antagonist haloperidol (HAL; 3 mg) or the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg), on separate sessions before a 15-minute slot machine game or amphetamine (AMPH; 20 mg), in a placebo-controlled, double-blind, counterbalanced design.
On their own, HAL and FLU led to linear increases and decreases, respectively, in desire to gamble across increasing levels of impulsivity. The slot machine and AMPH each evoked an inverted-U pattern of desire to gamble across increasing impulsivity. HAL reversed this effect of the game, whereas FLU did not alter post-game desire. HAL and FLU decreased and increased psychostimulant-like effects of the game, respectively, in LI and MI subjects, but consistently reduced these effects in HI subjects. HAL also altered the salience of negative affective words on a reading task, such that greater salience of negative words coincided with lower post-game desire to gamble.
D1 receptors appear to gauge the incentive value of gambling in GD subjects. D1 activation has negative reinforcing effects in HI gamblers and positive reinforcing effects in LI gamblers. Medications that activate D1 could curtail chasing in HI gamblers. D1 blockade could benefit HI gamblers whose main concern is craving.
多巴胺 D1 和 D2 受体在赌博障碍（GD）中的功能作用仍不清楚。
本研究旨在探讨 D1 激活的作用，以及与较弱的 D2 介导的多巴胺释放抑制相关的冲动特质的调节作用，在 GD 患者中的作用。
30 名（9 名女性）非共患 GD 患者，低（LI）、中（MI）或高冲动（HI），在单独的会议上分别接受选择性 D2 拮抗剂氟哌啶醇（HAL；3mg）或混合 D1-D2 拮抗剂氟奋乃静（FLU；3mg），在一个安慰剂对照、双盲、交叉平衡的设计之前，进行 15 分钟的老虎机游戏或安非他命（AMPH；20mg）。
单独使用时，HAL 和 FLU 分别导致在冲动性增加的情况下，对赌博的渴望呈线性增加和减少。老虎机和 AMPH 在冲动性增加的情况下，分别诱发了赌博欲望的倒 U 型模式。HAL 逆转了游戏的这种效果，而 FLU 并没有改变游戏后的渴望。HAL 和 FLU 分别降低和增加了游戏的精神兴奋剂样作用，在 LI 和 MI 患者中，但在 HI 患者中一致降低了这些作用。HAL 还改变了阅读任务中消极情绪词的显著性，使得消极词的显著性越高，游戏后的赌博欲望越低。
D1 受体似乎可以衡量 GD 患者赌博的激励价值。D1 激活在 HI 赌徒中具有负强化作用，在 LI 赌徒中具有正强化作用。激活 D1 的药物可以遏制 HI 赌徒的追逐。D1 阻断可能有益于 HI 赌徒，他们的主要关注点是渴望。
