Department of Psychology, University of British Columbia, Vancouver.
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, Ontario, Canada; Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Pharmacology, Family and Community Medicine, and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Biol Psychiatry. 2014 May 15;75(10):817-24. doi: 10.1016/j.biopsych.2013.08.026. Epub 2013 Oct 4.
Cognitive distortions regarding gambling outcomes confer vulnerability to pathological gambling. Using a rat slot machine task (rSMT), we previously demonstrated that the nonspecific D₂ agonist quinpirole enhances erroneous expectations of reward on near-miss trials, suggesting a pivotal role for the D₂ receptor family in mediating the near-miss effect. Identifying which receptor subtype is involved could facilitate treatment development for compulsive slot machine play.
Thirty-two male Long Evans rats learned the rSMT. Three flashing lights could be set to on or off. A win was signaled if all three lights were set to on, whereas any other light pattern indicated a loss. Rats then chose between responding on the collect lever, which delivered 10 sugar pellets on win trials but a 10-second time penalty on loss trials, or to start a new trial instead. Performance was assessed following systemic administration of selective D₂, D₃, and D₄ receptor ligands.
The selective D₂ antagonist L-741,626, the D₃ antagonist SB-277011-A, and the D₃ agonist PD128,907 had no effect. In contrast, the selective D₄ agonist PD168077 partially mimicked quinpirole's effects, increasing erroneous collect responses on nonwin trials, whereas the D₄ antagonist L-745,870 improved the error rate. L-745,870 was also the only antagonist that could attenuate the deleterious effects of quinpirole.
The dopamine D₄ receptor is critically involved in signaling reward expectancy in the rSMT. The ability of L-745,870 to reduce the classification of losses as wins suggests that D₄ antagonists could be effective in treating problematic slot machine play.
关于赌博结果的认知扭曲会导致病理性赌博的易感性。我们之前使用大鼠老虎机任务（rSMT）表明，非特异性 D₂ 激动剂喹吡罗增强了近失试验中错误的奖励期望，这表明 D₂ 受体家族在介导近失效应中起着关键作用。确定涉及的受体亚型可以促进治疗强迫性老虎机游戏的发展。
32 只雄性长耳兔学习 rSMT。三个闪光灯可以设置为开或关。如果所有三个灯都设置为开，则表示赢，而任何其他灯光模式表示输。然后，大鼠可以选择在收集杆上做出反应，赢时可获得 10 个糖丸，但输时则会有 10 秒的时间惩罚，或者选择开始新的试验。在系统给予选择性 D₂、D₃和 D₄ 受体配体后评估性能。
选择性 D₂ 拮抗剂 L-741,626、D₃ 拮抗剂 SB-277011-A 和 D₃ 激动剂 PD128,907 没有效果。相比之下，选择性 D₄ 激动剂 PD168077 部分模拟了喹吡罗的作用，增加了非赢试验中的错误收集反应，而 D₄ 拮抗剂 L-745,870 则提高了错误率。L-745,870 也是唯一能够减弱喹吡罗有害作用的拮抗剂。
多巴胺 D₄ 受体在 rSMT 中对信号传递奖励期望至关重要。L-745,870 能够减少将损失归类为胜利的能力表明，D₄ 拮抗剂可能对治疗有问题的老虎机游戏有效。
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