Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder
Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder
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DOI：
10.1186/1744-9081-8-10
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发表时间：
2012-02-28
影响因子：
5.1
通讯作者：
Lei, Ge-fei
中科院分区：
文献类型：
--
作者：
Cao, Ai-hua;Yu, Lin;Lei, Ge-fei
背景资料：虽然赤字的注意定势转移已被报道在个人与注意缺陷/多动症（ADHD），它很少在动物models.Methods：本研究比较了自发性高血压大鼠（SHR; ADHD的遗传动物模型）和Wistar-Kyoto（WKY）和Sprague-Dawley（SD）大鼠（normoactive控制株），注意定势转移任务（ASST）的性能。此外，还研究了哌甲酯（MPH）对自发性高血压大鼠注意定势转移的剂量效应。实验一：对5周龄SHR、WKY和SD大鼠各8只进行ASST。记录初始阶段的平均延迟、错误类型和数量以及每个阶段的标准试验。在实验2中，24只SHR大鼠被随机分配到3组，每组8只- MPH-L（低剂量）、MPH-H（高剂量）和SHR溶剂组。从第3周开始，分别给予2.5mg/kg或5 mg/kg MPH或生理盐水，连续14天。结果：自发性高血压大鼠在ASST中的表现普遍低于对照组WKY和SD大鼠。观察到对平均潜伏期[F（2，21）= 639.636，p < 0.001]和标准试验[F（2，21）= 114.118，p < 0.001]的显著应变效应。SHR的持续性和回归性错误率均高于对照品系（p < 0.001）。在MPH处理后，两个MPH处理组表现出比SHR-媒介物组显著更长的潜伏期和更少的达到标准的试验，并且与MPH-H组相比，MPH-L组在更多阶段表现出更少的达到标准的试验。治疗主效应[F（2，21）= 52.174，p < 0.001]和错误类型主效应[F（2，42）= 221.635，p < 0.01]显著。我们的研究结果表明MPH可以改善SHR的注意定势转换，并且低剂量的MPH比高剂量的MPH更有效。
Background: Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models.Methods: This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks.Results: The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found.Conclusions: The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.