The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD.
The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD.
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DOI：
10.3389/fnbeh.2015.00326
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发表时间：
2015
影响因子：
3
通讯作者：
Shiflett MW
中科院分区：
文献类型：
--
作者：
Natsheh JY;Shiflett MW
虽然注意缺陷多动障碍（ADHD）的注意力和运动改变已经被很好地描述，但这种疾病如何影响目标导向行为却鲜为人知。为了研究ADHD动物模型中目标导向行为和习惯行为之间是否存在失衡，我们对成年自发性高血压大鼠(SHR；ADHD大鼠模型)和Wistar-Kyoto大鼠（WKY）（正常对照品系）在两个阶段的工具条件作用范式上进行了研究：一个是自由操作训练阶段，大鼠分别获得两种不同的动作-结果偶然性，另一个是在灭绝之前进行的选择测试，其中一种食物结果通过特定饱腹感而贬值。为了评估哌醋甲酯（一种常用的ADHD药物）对目标导向行为的影响，我们在选择测试前给大鼠注射哌醋甲酯或生理盐水。两种大鼠品系都获得了工具性反应，在训练过程中，SHR的反应率更高。在选择测试中，WKY表现出目标导向的行为，在训练期间，更频繁地对交付的杠杆做出反应，仍然有价值的结果。相比之下，SHR没有表现出目标导向的行为，对两种杠杆的反应相同。然而，在选择测试之前给药MPH恢复了SHR的目标导向行为，并破坏了WKY大鼠的这种行为。本研究为ADHD大鼠模型中目标导向行为的选择性损害提供了第一个实验证据，以及MPH分别对SHR和WKY动物恢复或损害这种行为的不同作用。
Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75–P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar–Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action–outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively.