首页> 外文期刊>Brain research. Developmental brain research >Methylphenidate differentially regulates c-fos and fosB expression in the developing rat striatum.
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Methylphenidate differentially regulates c-fos and fosB expression in the developing rat striatum.

机译:哌醋甲酯差异调节发育中的大鼠纹状体中c-fos和fosB的表达。

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Methylphenidate (MPH, Ritalin) is a psychostimulant drug used in very young children with attention deficit hyperactivity disorder (ADHD). To explore the central effects of MPH, we compared repeated MPH treatments on c-fos and fosB expression in the striatum of immature and adult rats. Prepubertal (PD25-38) or adult (PD53-66) male rats were treated once daily for: (a) 14 days with either saline or MPH (2 or 10 mg/kg) or (b) 13 days with saline followed by a single dose of MPH (2 or 10 mg/kg) on day 14. To determine long-term effects of MPH, another group of prepubertal rats was allowed a drug-free period of 4 weeks following the initial 14 days of treatment, and received a challenge dose of MPH at adulthood. All rats were sacrificed 2 h post-injection on the final day. Expression of c-fos and fosB was quantified by densitometric analysis of cFOS and FOSB-immunoreactivity (-ir). We demonstrated that FOSB-ir was increased by a single dose of MPH in the prepubertal and adult striatum, and this effect was further elevated by chronic MPH in prepubertal rats, in contrast to the inhibitory effect of MPH (2 and 10 mg/kg) on cFOS-ir. In adult rats, repeated MPH down-regulated cFOS-ir only at the higher dose (10 mg/kg), while fosB expression remained at levels comparable to acute MPH. The reduction in cFOS-ir observed in prepubertal rats given repeated MPH (10 mg/kg) persisted in the adult striatum following MPH challenge at adulthood. Our results suggest that (1) repeated MPH treatment differentially regulates c-fos and fosB expression in the immature and adult brain; (2) MPH-induced changes in gene expression may be enduring, and (3) the immature brain is more sensitive to the stimulant effects of MPH than the adult. Thus, our findings have implications for the long-term use of MPH in ADHD.
机译:哌醋甲酯(MPH,利他林)是一种精神刺激药,用于患有注意缺陷多动障碍(ADHD)的很小的孩子。为了探讨MPH的中心作用,我们比较了未成熟和成年大鼠纹状体中重复MPH处理对c-fos和fosB表达的影响。每天对青春期前(PD25-38)或成年(PD53-66)雄性大鼠进行以下治疗:(a)生理盐水或MPH(2或10 mg / kg)14天,或(b)生理盐水13天,然后进行生理盐水在第14天服用单剂量的MPH(2或10 mg / kg)。为确定MPH的长期作用,在开始治疗的第14天后,另一组青春期前大鼠被禁药4周,并接受成年后的MPH挑战剂量。在最后一天注射后2小时处死所有大鼠。通过对cFOS和FOSB免疫反应性(-ir)的光密度分析来量化c-fos和fosB的表达。我们证明,青春期前和成年纹状体中单剂量的MPH会增加FOSB-ir,而与MPH的抑制作用(2和10 mg / kg)相比,慢性MPH在青春期前的大鼠中会进一步提高这种作用。在cFOS-ir上。在成年大鼠中,重复的MPH仅在较高剂量(10 mg / kg)时才下调cFOS-ir,而fosB表达保持在与急性MPH相当的水平。在成年期进行MPH攻击后,在成年纹状体中,反复给予MPH(10 mg / kg)后,在青春期前大鼠中观察到的cFOS-ir降低仍然存在。我们的结果表明:(1)反复进行MPH处理可差异调节未成熟大脑和成年大脑中的c-fos和fosB表达; (2)MPH诱导的基因表达变化可能会持续存在;(3)未成熟的大脑对MPH的刺激作用比成年人更为敏感。因此,我们的发现对在多动症中长期使用MPH具有重要意义。

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