Dopaminergic lesions of the dorsolateral striatum in rats increase delay discounting in an impulsive choice task

Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors.

纹状体环路中多巴胺传递失调与冲动行为相关。本研究评估了背外侧纹状体（dorsolateral striatum）的多巴胺能输入对冲动选择——冲动行为的一个维度——的影响。我们采用了一项操作性任务，通过延迟折扣（delay discounting）范式评估大鼠的冲动选择行为，以颅内自我刺激（intracranial self-stimulation, ICSS）作为正性强化物。为此，我们对大鼠实施麻醉，在一侧半球的下丘脑外侧植入刺激电极，并向双侧背外侧纹状体注射多巴胺能毒素6-羟基多巴胺（6-OHDA，损伤组）或其溶媒（假手术组）。术后恢复阶段，大鼠接受延迟折扣任务训练：在按压杠杆后，大鼠可选择立即获得的小剂量ICSS电流，或是按压另一杠杆并经过0至15秒延迟后获得的大剂量ICSS电流。损伤组与假手术组大鼠的任务习得与强化物辨别能力无显著差异。所有大鼠初始均偏好大剂量强化物，随着延迟时长增加，大鼠对大剂量强化物的偏好逐渐降低，表明大剂量强化物的主观价值随延迟时间增长而被折扣。然而，在较长延迟条件下，损伤组大鼠的折扣效应显著增强。本研究结果揭示了背外侧纹状体的多巴胺能输入对冲动选择行为的调控作用，并为延迟折扣行为的神经底物提供了新的见解。