Adams David H, Hanson Glen R, Keefe Kristen A
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.
J Neurochem. 2003 Jan;84(1):87-93. doi: 10.1046/j.1471-4159.2003.01507.x.
We and others previously reported that equimolar doses of methamphetamine and cocaine differentially increase preprodynorphin mRNA in striatum: methamphetamine causes a patchy increase, whereas cocaine produces a more homogenous one. The current study directly examined whether this effect reflects differential induction in the patch-matrix division of striatum, as identified by micro opioid receptor immunohistochemistry. In addition, we determined whether doses of cocaine (30 mg/kg) and methamphetamine (2 mg/kg) that produced equivalent increases in extracellular dopamine differentially affected preprodynorphin mRNA expression in striatum of male, Sprague-Dawley rats. In both experiments, methamphetamine and cocaine differentially affected preprodynorphin mRNA in striatum after 3 h. The high, equimolar dose of methamphetamine selectively increased preprodynorphin mRNA in the patch division of rostral striatum, whereas cocaine increased preprodynorphin mRNA throughout patch and matrix divisions of striatum. In contrast, a dose of methamphetamine (2.0 mg/kg) that caused an increase in extracellular dopamine similar to that produced by 30 mg/kg cocaine did not significantly affect preprodynorphin mRNA in any region of striatum. These data provide further evidence that cocaine and amphetamines exert distinct effects on the patch-matrix division of striatum and suggest further that the post-synaptic consequences of elevated extracellular dopamine produced by methamphetamine and cocaine are distinct.
我们和其他研究人员之前报道过,等摩尔剂量的甲基苯丙胺和可卡因对纹状体中前强啡肽原mRNA的增加具有不同的影响:甲基苯丙胺会导致斑块状增加,而可卡因则产生更均匀的增加。本研究直接检测了这种效应是否反映了纹状体斑块-基质分区中的差异诱导,这是通过微阿片受体免疫组织化学鉴定的。此外,我们还确定了可卡因(30mg/kg)和甲基苯丙胺(2mg/kg)的剂量,这些剂量在细胞外多巴胺水平上产生了等效的增加,是否对雄性Sprague-Dawley大鼠纹状体中前强啡肽原mRNA的表达有不同的影响。在这两个实验中,甲基苯丙胺和可卡因在3小时后对纹状体中的前强啡肽原mRNA有不同的影响。高剂量等摩尔的甲基苯丙胺选择性地增加了纹状体前部斑块分区中的前强啡肽原mRNA,而可卡因则增加了纹状体整个斑块和基质分区中的前强啡肽原mRNA。相比之下,导致细胞外多巴胺增加程度与30mg/kg可卡因相似的甲基苯丙胺剂量(2.0mg/kg)对纹状体任何区域的前强啡肽原mRNA均无显著影响。这些数据进一步证明可卡因和苯丙胺对纹状体的斑块-基质分区有不同的作用,并进一步表明甲基苯丙胺和可卡因导致的细胞外多巴胺升高的突触后后果是不同的。