Kim Yong, Teylan Merilee A, Baron Matthew, Sands Adam, Nairn Angus C, Greengard Paul
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2915-20. doi: 10.1073/pnas.0813179106. Epub 2009 Feb 6.
Methylphenidate is the psychostimulant medication most commonly prescribed to treat attention deficit hyperactivity disorder (ADHD). Recent trends in the high usage of methylphenidate for both therapeutic and nontherapeutic purposes prompted us to investigate the long-term effects of exposure to the drug on neuronal adaptation. We compared the effects of chronic methylphenidate or cocaine (15 mg/kg, 14 days for both) exposure in mice on dendritic spine morphology and DeltaFosB expression in medium-sized spiny neurons (MSN) from ventral and dorsal striatum. Chronic methylphenidate increased the density of dendritic spines in MSN-D1 (MSN-expressing dopamine D1 receptors) from the core and shell of nucleus accumbens (NAcc) as well as MSN-D2 (MSN-expressing dopamine D2 receptors) from the shell of NAcc. In contrast, cocaine increased the density of spines in both populations of MSN from all regions of striatum. In general, the effect of methylphenidate on the increase of shorter spines (class 2) was less than that of cocaine. Interestingly, the methylphenidate-induced increase in the density of relatively longer spines (class 3) in the shell of NAcc was bigger than that induced by cocaine. Furthermore, methylphenidate exposure increased expression of DeltaFosB only in MSN-D1 from all areas of striatum, and surprisingly, the increase was greater than that induced by cocaine. Thus, our results show differential effects of methylphenidate and cocaine on neuronal adaptation in specific types of MSN in reward-related brain regions.
哌甲酯是治疗注意力缺陷多动障碍（ADHD）最常用的精神兴奋药物。近期，哌甲酯在治疗和非治疗用途方面的高使用趋势促使我们研究该药物暴露对神经元适应性的长期影响。我们比较了慢性给予小鼠哌甲酯或可卡因（均为15mg/kg，持续14天）对腹侧和背侧纹状体中中型棘状神经元（MSN）树突棘形态和DeltaFosB表达的影响。慢性给予哌甲酯可增加伏隔核（NAcc）核心和壳部的表达多巴胺D1受体的MSN（MSN-D1）以及NAcc壳部的表达多巴胺D2受体的MSN（MSN-D2）的树突棘密度。相比之下，可卡因可增加纹状体所有区域的两种MSN群体的树突棘密度。总体而言，哌甲酯对较短树突棘（2类）增加的影响小于可卡因。有趣的是，哌甲酯诱导的NAcc壳部相对较长树突棘（3类）密度增加大于可卡因诱导的增加。此外，哌甲酯暴露仅增加纹状体所有区域的MSN-D1中DeltaFosB的表达，令人惊讶的是，增加幅度大于可卡因诱导的增加。因此，我们的结果显示了哌甲酯和可卡因对奖励相关脑区特定类型MSN中神经元适应性的不同影响。
