Zhang Ying-Chun, Zhu Xue-Qing, Zhang Xue-Han
Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Sheng Li Xue Bao. 2017 Aug 25;69(4):378-384.
The etiology of attention-deficit hyperactivity disorder (ADHD) has been generally linked to the decrease in cortex activity, as well as to the reduction in dopamine (DA) and norepinephrine (NE) levels. Methylphenidate (MPH; Ritalin) is the most commonly prescribed medication for ADHD. It has been determined that MPH acts primarily on the dopaminergic and noradrenergic systems through blockade of DA and NE transporters, thereby increasing the concentrations of these neurotransmitters in the brain to correct the attention deficits and hyperactivity. In addition, MPH has been proposed to increase the excitability of pyramidal neurons and the overall activity of cortex. However, the effect of MPH on the activity of interneurons is lack of investigation. Here, by using immunohistochemistry technique, we examined c-Fos expression in parvalbumin (PV)-expressing interneurons of frontal cortex of rats (28-day-old) at 1 h after a single MPH infusion (1 or 8 mg/kg; s.c.). We analyzed the c-Fos expression in the medial orbitofrontal cortex (MO), ventral orbitofrontal cortex (VO), and lateral orbitofrontal cortex (LO) subregions of orbitofrontal cortex (OFC), as well as the prelimbic cortex (PrL) and infralimbic cortex (IL) subregions of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) after MPH infusion. Our data showed that MPH increased c-Fos expression in MO, VO and LO, and the c-Fos expression in PV-expressing interneurons elevated significantly in MO, VO, but not in LO. Meanwhile, the increases of c-Fos expression in PrL and IL, as well as in PV-expressing interneurons of these two regions, were only induced by 1 mg/kg MPH, but not 8 mg/kg. Both 1 and 8 mg/kg MPH dramatically increased c-Fos expression in ACC, especially, in PV-expressing interneurons of ACC as well. In conclusion, acute systemic injection of MPH significantly increases the c-Fos expression in PV-expressing interneurons of the OFC, PFC and ACC.
注意缺陷多动障碍（ADHD）的病因通常与皮质活动减少以及多巴胺（DA）和去甲肾上腺素（NE）水平降低有关。哌甲酯（MPH；利他林）是治疗ADHD最常用的药物。已确定MPH主要通过阻断DA和NE转运体作用于多巴胺能和去甲肾上腺素能系统，从而增加这些神经递质在大脑中的浓度，以纠正注意力缺陷和多动。此外，有人提出MPH可增加锥体神经元的兴奋性和皮质的整体活动。然而，MPH对中间神经元活动的影响尚缺乏研究。在此，我们通过免疫组织化学技术，检测了单次腹腔注射MPH（1或8mg/kg）1小时后，28日龄大鼠额叶皮质中表达小白蛋白（PV）的中间神经元的c-Fos表达。我们分析了眶额叶皮质（OFC）的内侧眶额叶皮质（MO）、腹侧眶额叶皮质（VO）和外侧眶额叶皮质（LO）亚区，以及前额叶皮质（PFC）的前边缘皮质（PrL）和下边缘皮质（IL）亚区和前扣带回皮质（ACC）在注射MPH后的c-Fos表达。我们的数据显示，MPH增加了MO、VO和LO中的c-Fos表达，并且在MO、VO中，表达PV的中间神经元中的c-Fos表达显著升高，但在LO中未升高。同时，仅1mg/kg的MPH可诱导PrL和IL以及这两个区域中表达PV的中间神经元的c-Fos表达增加，而8mg/kg则不能。1mg/kg和8mg/kg的MPH均可显著增加ACC中的c-Fos表达，尤其是ACC中表达PV的中间神经元中的c-Fos表达。总之，急性全身注射MPH可显著增加OFC、PFC和ACC中表达PV的中间神经元的c-Fos表达。
