Tedford Stephanie E, Persons Amanda L, Napier T Celeste
Department of Pharmacology, Rush University, Chicago, Illinois, United States of America; Center for Compulsive Behavior and Addiction, Rush University, Chicago, Illinois, United States of America.
Department of Pharmacology, Rush University, Chicago, Illinois, United States of America; Department of Psychiatry, Rush University, Chicago, Illinois, United States of America; Center for Compulsive Behavior and Addiction, Rush University, Chicago, Illinois, United States of America.
PLoS One. 2015 Apr 30;10(4):e0122063. doi: 10.1371/journal.pone.0122063. eCollection 2015.
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 15 s 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.
纹状体回路中多巴胺传递失调与冲动性有关。本研究评估了多巴胺能输入到背外侧纹状体对冲动选择(冲动行为的一个方面)的影响。我们实施了一项操作性任务,通过延迟折扣来测量大鼠的冲动选择,其中颅内自我刺激(ICSS)被用作正强化物。为此,将大鼠麻醉,以便在一个半球的外侧下丘脑内植入刺激电极,并对双侧背侧纹状体注射多巴胺能毒素6-羟基多巴胺(损伤组)或其载体(假手术组)。恢复后,对大鼠进行延迟折扣任务训练,在此任务中,它们要在按压杠杆后立即出现的小ICSS电流和按压另一杠杆后延迟0至15秒出现的大ICSS电流之间进行选择。损伤组和假手术组大鼠在任务习得和强化物辨别方面相似。所有大鼠最初都偏好大强化物,并且随着延迟时间增加,对大强化物的偏好降低,这表明大强化物的主观价值随着延迟时间而降低。然而,对于较长延迟,损伤组大鼠的这种折扣效应显著增强。这些数据揭示了多巴胺能输入到背外侧纹状体对冲动选择行为的作用,并为折扣行为的神经基础提供了新的见解。