Prior exposure to abused drugs leads to long-lasting neuroadaptations culminating in excessive drug intake. Given the comorbidity between substance use and gambling disorders, surprisingly little is known about the effects of exposure to reinforcement contingencies experienced during games of chance. As it is a central feature of these games, we characterized the effects of exposure to uncertainty on biochemical and behavioral effects normally observed in rats exposed to amphetamine. Rats in different groups were trained to nose-poke for saccharin under certain [fixed-ratio (FR)] or uncertain conditions [variable-ratio (VR)] for 55 1-h sessions. Ratios were escalated on successive sessions and rats maintained on the last ratio (FR/VR 20) for 20-25 days. Two to three weeks later, rats were tested for their locomotor or nucleus accumbens dopamine (NAcc DA) response to amphetamine or self-administration of the drug using a lever press operant. NAcc DA overflow was also assessed in additional rats during the saccharin sessions. Rats exposed to uncertainty subsequently showed a higher locomotor and NAcc DA response to amphetamine and self-administered more drug infusions relative to rats exposed to predictable reinforcement. NAcc DA levels during the saccharin sessions tracked the variance of the scheduled ratios (a measure of uncertainty). VR rats showed escalating DA overflow with increasing ratios. Exposure to uncertainty triggered neuroadaptations similar to those produced by exposure to abused drugs. As these were produced in drug naive rats both during and after exposure to uncertainty, they provide a novel common pathway to drug and behavioral addictions.

中文翻译：

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暴露在不确定的条件下会促进对苯丙胺的追求。

先前接触滥用药物会导致长期的神经适应，最终导致过量的药物摄入。考虑到物质使用和赌博障碍之间的共病，令人惊讶的是，人们对在机会游戏中经历的强化突发事件的影响知之甚少。由于它是这些游戏的核心特征，我们描述了暴露于不确定性对暴露于苯丙胺的大鼠中通常观察到的生化和行为影响的影响。训练不同组的大鼠在某些 [固定比率 (FR)] 或不确定条件 [可变比率 (VR)] 下用鼻子戳糖精 55 次，每次 1 小时。比率在连续会话中升级，大鼠在最后一个比率 (FR/VR 20) 上维持 20-25 天。两三个星期后，测试大鼠的运动或伏隔核多巴胺 (NAcc DA) 对安非他明的反应或使用杠杆按压操作的药物自我给药。NAcc DA 溢出还在糖精会议期间在其他大鼠中进行了评估。与暴露于可预测强化的大鼠相比，暴露于不确定性的大鼠随后表现出对安非他明的更高的运动和 NAcc DA 反应，并且自我给药更多的药物输注。糖精会议期间的 NAcc DA 水平跟踪预定比率的方差（不确定性的度量）。VR 大鼠表现出随着比率的增加，DA 溢出不断增加。暴露于不确定性会引发类似于暴露于滥用药物所产生的神经适应。由于这些是在暴露于不确定性期间和之后在未吸毒的大鼠中产生的，