Gambling disorder (GD) is a behavioral addiction that may be linked to alterations in dopamine (DA) systems. Gambling involves chronic exposure to uncertain reward, which can sensitize the activity of DA systems. Here we explored how combinations of Pavlovian and instrumental uncertainty impact DA sensitization and risky decision-making. Experiment 1: 40 rats underwent 66 uncertainty exposure (UE) sessions during which they responded for saccharin. Animal responding was reinforced according to a fixed or variable (FR/VR) ratio schedule that turned on a conditioned stimulus (CS; light), which predicted saccharin on 50% or 100% of trials. Animals responded under one of the four conditions: FR-CS100% (no uncertainty), VR-CS100%, FR-CS50%, and VR-CS50% (maximal uncertainty). DA sensitization was inferred from an enhanced locomotor response to d-amphetamine (d-AMPH; 0.5 mg/kg) challenge. The rat gambling task (rGT) was used to assess decision-making. Experiment 2: 24 rats received 5 weeks of sensitizing d-AMPH or saline doses, followed by locomotor activity and rGT testing. Experiment 3: Effects of UE and a sensitizing d-AMPH regimen on DA D1, D2, and D3 receptor binding were assessed in 44 rats using autoradiography. Compared to FR-CS100%, VR-CS100% and VR-CS50% rats displayed a greater locomotor response to d-AMPH, and VR-CS50% rats demonstrated riskier decision-making. Chronic d-AMPH-treated rats mirrored the effects of VR-CS50% groups on these two indices. Both VR-CS50% and d-AMPH-treated groups had increased striatal DA D2 receptor binding. These results suggest that chronic uncertainty exposure, similar to exposure to a sensitizing d-AMPH regimen, sensitized the function of DA systems and increased risky decision-making.

中文翻译：

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暴露于长期不确定性和安非他明注射敏化方案对大鼠运动、决策和多巴胺受体的影响。


赌博障碍 (GD) 是一种行为成瘾，可能与多巴胺 (DA) 系统的改变有关。赌博涉及长期接触不确定的奖励，这可能会使 DA 系统的活动变得敏感。在这里，我们探讨了巴甫洛夫不确定性和工具不确定性的组合如何影响 DA 敏感性和风险决策。实验 1：40 只大鼠经历了 66 次不确定性暴露 (UE) 疗程，在此期间它们对糖精有反应。根据开启条件刺激（CS；光）的固定或可变（FR/VR）比率方案来强化动物反应，该方案在 50% 或 100% 的试验中预测糖精。动物在以下四种条件之一下做出反应：FR-CS100%（无不确定性）、VR-CS100%、FR-CS50% 和 VR-CS50%（最大不确定性）。 DA 致敏是通过对 d-安非他明（d-AMPH；0.5 mg/kg）激发的运动反应增强来推断的。大鼠赌博任务（rGT）用于评估决策。实验2：24只大鼠接受5周的致敏d-AMPH或盐水剂量，随后进行运动活动和rGT测试。实验3：使用放射自显影术在44只大鼠中评估UE和敏化d-AMPH方案对DA D1、D2和D3受体结合的影响。与 FR-CS100% 相比，VR-CS100% 和 VR-CS50% 大鼠对 d-AMPH 表现出更强的运动反应，VR-CS50% 大鼠表现出更高风险的决策。慢性 d-AMPH 治疗的大鼠反映了 VR-CS50% 组对这两个指数的影响。 VR-CS50% 和 d-AMPH 治疗组的纹状体 DA D2 受体结合增加。这些结果表明，与暴露于致敏 d-AMPH 方案类似，长期暴露于不确定性会使 DA 系统的功能变得敏感并增加风险决策。