Wang J Q, Smith A J, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.
Neuroscience. 1995 Sep;68(1):83-95. doi: 10.1016/0306-4522(95)00100-w.
In this study, the effects of a single dose of the indirect dopamine agonists amphetamine and methamphetamine on behavior and messenger RNA expression were evaluated. Expression of c-fos, a member of the leucine zipper family, zif/268 (NGFI-A, egr1 and Krox-24), a member of the zinc finger family, and the opioid peptide, preprodynorphin, was investigated in various regions of rat forebrain with quantitative in situ hybridization histochemistry 1, 2, 3, 6 or 30 h after injection. Behavioral observations indicated that a qualitatively different behavioral syndrome was induced following methamphetamine (15 mg/kg, i.p.) as compared with that observed after amphetamine (5 mg/kg, i.p.). Similarly, methamphetamine induced a different pattern of c-fos and zif/268 messenger RNA induction in sensory/motor cortex, dorsal striatum (caudatoputamen) and ventral striatum (nucleus accumbens) than did amphetamine. The increase in c-fos messenger RNA expression peaked at 1 h and returned to basal levels in all regions by 3 h. In contrast, the increase in zif/268 messenger RNA expression in the cortical regions was equally strong at 1 and 2 h, gradually returning to basal levels by 6 h after either drug. However, in the striatal regions, zif/268 messenger RNA levels peaked at 1 h and declined gradually to basal levels by 6 h. Interestingly, methamphetamine caused an actual suppression of zif/268 gene expression (> 50%) in both caudatoputamen and nucleus accumbens at 3 h. Preprodynorphin messenger RNA expression was increased in a patchy motif in the caudatoputamen and nucleus accumbens beginning at 2 h and returning to basal levels by 30 h after injection of either drug. This study, together with our recently published observation that preprodynorphin messenger RNA is induced in the caudate 3, 6 and 18 h after amphetamine or methamphetamine injection, provides a detailed dynamic description of the differential modulation of c-fos, zif/268 and preprodynorphin messenger RNA expression in the cerebral cortex and striatum by amphetamines over time. These data implicate immediate early gene and preprodynorphin gene expression in the differential response of medium spiny striatal neurons to methamphetamine and amphetamine.
在本研究中，评估了单剂量间接多巴胺激动剂苯丙胺和甲基苯丙胺对行为和信使核糖核酸（mRNA）表达的影响。在注射后1、2、3、6或30小时，采用定量原位杂交组织化学方法，研究了大鼠前脑各区域中亮氨酸拉链家族成员c-fos、锌指家族成员zif/268（NGFI-A、egr1和Krox-24）以及阿片肽前强啡肽原的表达。行为观察表明，与注射苯丙胺（5mg/kg，腹腔注射）后观察到的情况相比，注射甲基苯丙胺（15mg/kg，腹腔注射）后诱发了一种性质不同的行为综合征。同样，甲基苯丙胺在感觉/运动皮层、背侧纹状体（尾状核壳核）和腹侧纹状体（伏隔核）中诱导的c-fos和zif/268信使核糖核酸诱导模式与苯丙胺不同。c-fos信使核糖核酸表达的增加在1小时达到峰值，并在3小时时在所有区域恢复到基础水平。相比之下，两种药物注射后，皮层区域zif/268信使核糖核酸表达在1小时和2小时时同样强烈，在6小时时逐渐恢复到基础水平。然而，在纹状体区域，zif/268信使核糖核酸水平在1小时达到峰值，并在6小时时逐渐下降到基础水平。有趣的是，在3小时时，甲基苯丙胺在尾状核壳核和伏隔核中实际抑制了zif/268基因表达（>50%）。注射任何一种药物后，前强啡肽原信使核糖核酸表达在尾状核壳核和伏隔核中以斑片状模式增加，从2小时开始，在30小时时恢复到基础水平。本研究以及我们最近发表的观察结果，即注射苯丙胺或甲基苯丙胺后3、6和18小时尾状核中前强啡肽原信使核糖核酸被诱导，提供了苯丙胺随时间对大脑皮层和纹状体中c-fos、zif/268和前强啡肽原信使核糖核酸表达的差异调节的详细动态描述。这些数据表明即刻早期基因和前强啡肽原基因表达与中等棘状纹状体神经元对甲基苯丙胺和苯丙胺的差异反应有关。
