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目前已知注意力缺损多动症(attention-deficit hyperactivity disorder,ADHD)的发病机制与额叶皮层活动降低、多巴胺(dopamine,DA)和去甲肾上腺素(norepinephrine,NE)不足有关。利他林目前是临床治疗ADHD的首选使用药物。它是单胺类递质转运体抑制剂,通过阻断转运体,提高细胞外DA和NE浓度,达到治疗效果。除此之外,利他林还可以增强皮层锥体神经元的兴奋性,增强皮层整体的活动。但是,利他林对中间神经元活动的影响尚不清楚。本研究采用药理学和免疫组织化学技术,探讨全身注射利他林对幼年大鼠眶额皮层(orbitofrontal cortex,OFC)、前额叶皮层(prefrontal cortex,PFC)和前扣带皮层(anterior cingulate cortex,ACC)中小清蛋白(parvalbumin,PV)阳性中间神经元c-Fos表达的影响。结果显示,利他林显著增加OFC的内侧区(MO)、腹侧区(VO)和外侧区(LO)c-Fos的表达,但是仅增加MO区和VO区PV阳性中间神经元c-Fos的表达,对LO区PV阳性中间神经元c-Fos表达没有影响;对PFC前边缘区(Pr L)和缘下回区(IL)的分析显示,只有剂量为1 mg/kg的利他林可使这两个区域c-Fos的表达和PV阳性中间神经元c-Fos的表达明显增多,而8 mg/kg的利他林则无显著作用。利他林可使ACC中c-Fos的表达和PV阳性中间神经元c-Fos的表达显著增多。以上结果表明,对幼年大鼠全身给予利他林,可以激活其额叶皮层PV阳性中间神经元,提示利他林可能通过激活皮层PV阳性神经元调控皮层锥体神经元动作电位的发放和神经元网络的同步活动,影响皮层的输出。
It is known that the pathogenesis of attention-deficit hyperactivity disorder (ADHD) is related to the decrease of frontal cortex activity, the deficiency of dopamine (DA) and norepinephrine (NE). Ritalin is currently the drug of choice for the treatment of ADHD. It is a monoamine neurotransmitter inhibitor, by blocking the transporter, increasing the concentration of extracellular DA and NE to achieve the therapeutic effect. In addition, Ritalin can also enhance the excitability of cortical pyramidal neurons and enhance the overall cortical activity. However, the influence of Ritalin on the activity of interneurons is not clear. In this study, pharmacological and immunohistochemical techniques were used to investigate the effects of systemic injection of Ritalin on orbitofrontal cortex (OFC), prefrontal cortex (PFC) and anterior cingulate cortex (ACC) ) C-Fos expression in parvalbumin (PV) positive interneurons. The results showed that Ritalin significantly increased the expression of c-Fos in medial area (MO), ventral area (VO) and lateral area (LO) of OFC, but only increased the c-Fos in PV-positive interneurons , And had no effect on the expression of c-Fos in the PV-positive interneurons in the LO area. Analysis of the PrL and the marginal zone of the PFC revealed that only Ritalin at a dose of 1 mg / kg The expression of c-Fos and c-Fos in PV-positive interneurons increased obviously in these two regions, but no significant effect was observed in 8 mg / kg of Ritalin. Ritalin can significantly increase the expression of c-Fos and the expression of c-Fos in PV positive interneuron in ACC. These results indicated that the systemic administration of Ritalin to young rats could activate PV-positive interneurons in the frontal cortex, suggesting that Ritalin could regulate the action potential distribution of cortical pyramidal neurons by activating cortical PV-positive neurons and neuronal networks The synchronization activity affects the cortical output.