School of Biosciences, Cardiff University, Wales, UK.
Brain Res Bull. 2012 Jun 1;88(2-3):251-60. doi: 10.1016/j.brainresbull.2011.04.002. Epub 2011 Apr 15.
In order to provide an animal model of the impulsivity observed in Huntington's disease, the effects of bilateral neostriatal lesions in rats were evaluated in an operant delayed reinforcement task. When given a choice between responding to one lever for a small but immediate reward and a second lever for a larger delayed reward, normal rats exhibit a marked preference for responding to the high reward lever when the imposed delay is short, but progressively choose the lever associated with immediate small reward as the delays increase. Following striatal lesions, the animals continue to express similar preferences, but the lesions initially impose a distinct flattening of the delay-preference function, suggesting a relative insensitivity to the increasing delay parameter in making their response choices. However, this deficit declines with extend retraining on the task, such that 1-2 months after lesion the delay-dependent shift of preference from the delayed to the immediate lever as the delays lengthened was comparable in lesion and sham animals. Amphetamine further disinhibited all animals, apparent as a further increase in the number and reduction of the latencies of responses made to the lever associated with immediate reward. Striatal lesions had little influence on the effects of amphetamine on task performance, other than the increase in the numbers of omissions of lever and panel responses induced by the drug was more marked in the lesion than sham animals, and the lesioned animals exhibited less delay-dependency than the controls in their preference for responding to the lever associated with the larger delayed reinforcement at the highest (1.5 mg/kg) dose tested. The present results indicate small but clear effects of dorsal striatal lesions in an operant delayed reinforcement task, suggestive of an initial impairment in response selection and a reduction in their sensitivity to the delay interval itself. This deficit recovered with further training, which may be dependent upon relearning choice response procedures disrupted by the lesion, but might be reinstated by treatment with stimulant drugs. This article is part of a special issue entitled 'Behavioural, Anatomical, and Genetic Characterisation of Mouse and Rat Models of Huntington's Disease.'
为了提供亨廷顿病中观察到的冲动性的动物模型，评估了大鼠双侧新纹状体损伤在操作性延迟强化任务中的作用。当大鼠在一个杠杆上反应可以获得小但即时的奖励，而在另一个杠杆上反应可以获得更大的延迟奖励之间进行选择时，正常大鼠在延迟时间较短时，明显更喜欢对高奖励杠杆做出反应，但随着延迟时间的增加，逐渐选择与即时小奖励相关的杠杆。纹状体损伤后，动物继续表现出类似的偏好，但损伤最初使延迟偏好函数明显变平，表明在做出反应选择时对增加的延迟参数相对不敏感。然而，这种缺陷随着在任务上的扩展再训练而逐渐减少，以至于在损伤后 1-2 个月，当延迟时间延长时，从延迟到即时杠杆的偏好依赖性转移与假手术动物相当。安非他命进一步解除了所有动物的抑制，表现为对与即时奖励相关的杠杆的反应数量增加，反应潜伏期缩短。纹状体损伤对安非他命对任务表现的影响影响不大，除了药物引起的对杠杆和面板反应的漏反应数量增加更为明显外，损伤动物在对与最高（1.5mg/kg）剂量测试的更大延迟强化相关的杠杆的反应偏好方面的延迟依赖性低于对照组。这些结果表明，在操作性延迟强化任务中，背侧纹状体损伤有轻微但明显的影响，提示在反应选择方面存在初始损伤，并且对延迟间隔本身的敏感性降低。这种缺陷随着进一步的训练而恢复，这可能依赖于由于损伤而中断的选择反应程序的重新学习，但可能通过兴奋剂药物的治疗而恢复。本文是题为“亨廷顿病的小鼠和大鼠模型的行为、解剖和遗传特征”的特刊的一部分。
