Response inhibition is a critical executive control function in many species. Deficits in response inhibition have been observed in many disorders, eg, attention deficit/hyperactivity disorder (ADHD). The stop-signal task (SST) is a unique behavior task for evaluating response inhibition via measuring the covert latency of a stop process, and it is widely used in studies of humans, nonhuman primates and rodents. Methylphenidate (MPH; Ritalin^®) is a psychostimulant that is widely used for the treatment of ADHD and that effectively improves response inhibition in individuals with ADHD and normal subjects. However, its mechanism of improving response inhibition remains unknown. In this study we adopted a rodent nose-poking version of the SST to examine response inhibition by estimating the stop signal reaction time (SSRT) in rats. Administration of MPH (1 mg/kg, sc) 25 min before the SST test exerted a baseline-dependent effect of MPH on response inhibition, ie, it shortened the SSRTs only in the rats with larger baseline SSRTs, thereby improving response inhibition in these rats. The effect of MPH on response inhibition remained 3 h after MPH administration. Co-administration of PP2 (1 mg/kg, sc), a Src-protein tyrosine kinase (Src-PTKs) inhibitor that inhibited the upregulation of glutamate receptor expression on the plasma membrane of the prefrontal cortex (PFC), abolished the MPH-caused improvement in response inhibition. Furthermore, intra-PFC infusion of a selective AMPAR antagonist.NASPM (0.3 mmol/L, per side) via stainless guide cannulas implanted earlier abolished the effect of MPH on SSRT. These results suggest that AMPA receptors in the PFC are involved in the effect of MPH on response inhibition in rats.

中文翻译：

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前额叶AMPA受体参与了哌醋甲酯对大鼠反应抑制的作用。

在许多物种中，反应抑制是关键的执行控制功能。在许多疾病中，例如在注意力缺陷/多动症（ADHD）中，观察到了反应抑制的不足。停止信号任务（SST）是一种独特的行为任务，用于通过测量停止过程的隐性潜伏期来评估响应抑制，它已广泛用于人类，非人类灵长类动物和啮齿动物的研究。哌醋甲酯（MPH;利他林^®）是一种精神刺激药，广泛用于治疗ADHD，并有效改善ADHD个体和正常受试者的反应抑制。但是，其改善反应抑制的机制仍是未知的。在这项研究中，我们采用了SST的啮齿动物的鼻子戳法，通过估计大鼠的停止信号反应时间（SSRT）来检查反应抑制。在SST测试前25分钟服用MPH（1 mg / kg，sc）发挥MPH对反应抑制的基线依赖性作用，即，仅在基线SSRT较大的大鼠中缩短了SSRT，从而改善了这些患者的反应抑制大鼠。MPH给药后3小时，MPH对应答抑制的作用仍然存在。PP2（1 mg / kg，sc）的共同给药，一种Src蛋白酪氨酸激酶（Src-PTKs）抑制剂，可抑制前额叶皮质（PFC）质膜上谷氨酸受体表达的上调，从而消除了MPH引起的反应抑制改善。此外，通过较早植入的不锈钢引导插管在PFC内输注选择性AMPAR拮抗剂NASPM（每侧0.3 mmol / L）消除了MPH对SSRT的影响。这些结果表明，PFC中的AMPA受体参与了MPH对大鼠反应抑制的作用。