Deficits in cost/benefit decision making is a critical risk factor for gambling disorder. Reward-paired cues may play an important role, as these stimuli can enhance risk preference in rats. Despite extensive research implicating the dorsal striatum in the compulsive aspects of addiction, the role of nigrostriatal dopaminergic activity in cue-induced risk preference remains unclear, particularly in females. Accordingly, we examined the effects of manipulating the dopaminergic nigrostriatal pathway on cue-induced risky choice in female rats. TH:Cre rats were trained on the cued version of the rat Gambling Task. This task was designed such that maximal reward is attained by avoiding the high-risk, high-reward options and instead favouring the options associated with lower per-trial gains, as they feature less frequent and shorter time-out penalties. Adding reward-paired audiovisual cues to the task leads to greater risky choice on average. To assess the role of the nigrostriatal pathway, a viral vector carrying either Cre-dependent inhibitory or excitatory DREADD was infused into the substantia nigra. Rats then received clozapine-N-oxide either during task acquisition or after a stable performance baseline was reached. Inhibition of this pathway accelerated the development of risk preference in early sessions and increased risky choice during performance, but long-term inhibition actually improved decision making. Activation of this pathway had minimal effects. These results provide evidence for the involvement of the dopaminergic nigrostriatal pathway in cue-induced risk preference in females, therefore shedding light on its role in cost/benefit decision-making deficits and expanding our knowledge of the female dopaminergic system.

中文翻译：

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黑质纹状体通路中的多巴胺活性改变雌性大鼠线索诱导的风险选择模式

成本/收益决策的缺陷是赌博障碍的一个关键风险因素。奖励配对线索可能发挥重要作用，因为这些刺激可以增强大鼠的风险偏好。尽管大量研究表明背侧纹状体与成瘾的强迫方面有关，但黑质纹状体多巴胺能活动在提示诱导的风险偏好中的作用仍不清楚，特别是在女性中。因此，我们研究了操纵多巴胺能黑质纹状体通路对雌性大鼠提示诱导的风险选择的影响。 TH：Cre 大鼠接受了提示版本的大鼠赌博任务的训练。这项任务的设计目的是通过避免高风险、高回报的选项，而是选择与每次试验收益较低相关的选项来获得最大奖励，因为它们的特点是频率较低、超时惩罚较短。在任务中添加奖励配对的视听提示平均会导致更大的风险选择。为了评估黑质纹状体通路的作用，将携带 Cre 依赖性抑制性或兴奋性 DREADD 的病毒载体注入黑质。然后，大鼠在任务获取期间或达到稳定的性能基线后接受氯氮平-N-氧化物。对该通路的抑制加速了早期风险偏好的发展，并增加了表演过程中的风险选择，但长期抑制实际上改善了决策。该途径的激活影响很小。这些结果为多巴胺能黑质纹状体通路参与女性提示诱导的风险偏好提供了证据，因此揭示了其在成本/收益决策缺陷中的作用，并扩大了我们对女性多巴胺能系统的了解。