Wang J Q, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina, USA.
J Neurochem. 1995 Dec;65(6):2706-15. doi: 10.1046/j.1471-4159.1995.65062706.x.
This study investigated the hypothesis that D1 and D2 dopamine receptors interact to regulate the expression of zif/268 mRNA in rat forebrain after an acute injection of amphetamine or methamphetamine. Forty-five minutes and 3 h after a single injection of amphetamine (4 mg/kg i.p.) or methamphetamine (4 mg/kg i.p.), the mRNA expression of zif/268 in dorsal striatum and sensorimotor cortex was increased, as revealed by quantitative in situ hybridization histochemistry. Induction was more intense in striatal patches at 45 min than at 3 h, when a more homogeneous pattern of zif/268 mRNA induction was observed. SCH 23390, a selective D1 receptor antagonist, suppressed, and eticlopride, a D2 receptor antagonist, elevated, constitutive zif/268 mRNA levels in the striatum, but neither antagonist had a significant effect on the constitutive expression of zif/268 in soensorimotor cortex. Pretreatment with SCH 23390 completely blocked the stimulant-induced zif/268 expression in striatum and partially blocked the stimulant-induced zif/268 expression in cortex. Pretreatment with eticlopride augmented zif/268 mRNA expression in patch and matrix compartments of dorsal and ventral striatum 45 min after amphetamine or methamphetamine injection. However, at 3 h, eticloprides completely blocked amphetamine- and methamphetamine-stimulated zif/268 mRNA in dorsomedial, but not dorsolateral, striatum. In addition, eticlopride partially blocked cortical zif/268 induction by both amphetamines. Both antagonists prevented stimulant-induced hyperlocomotion and stereotypies. These results demonstrate that D1 and D2 receptors in mesolimbic/mesostriatal pathways both regulate amphetamine- and methamphetamine-stimulated behaviors and zif/268 mRNA expression. Furthermore, the effect of D2 receptor blockade on zif/268 expression was found to be contingent on the time interval investigated after psychostimulant administration.
急性注射苯丙胺或甲基苯丙胺后，多巴胺D1和D2受体相互作用以调节大鼠前脑zif/268 mRNA的表达。单次注射苯丙胺（4mg/kg腹腔注射）或甲基苯丙胺（4mg/kg腹腔注射）后45分钟和3小时，定量原位杂交组织化学显示，背侧纹状体和感觉运动皮层中zif/268的mRNA表达增加。45分钟时，纹状体斑块中的诱导比3小时时更强烈，3小时时观察到zif/268 mRNA诱导模式更均匀。选择性D1受体拮抗剂SCH 23390抑制纹状体中组成型zif/268 mRNA水平，而D2受体拮抗剂依替必利则使其升高，但两种拮抗剂对感觉运动皮层中zif/268的组成型表达均无显著影响。用SCH 23390预处理可完全阻断纹状体中兴奋剂诱导的zif/268表达，并部分阻断皮层中兴奋剂诱导的zif/268表达。用依替必利预处理可增强苯丙胺或甲基苯丙胺注射后45分钟背侧和腹侧纹状体斑块和基质区室中zif/268 mRNA的表达。然而，在3小时时，依替必利完全阻断了背内侧纹状体（而非背外侧纹状体）中苯丙胺和甲基苯丙胺刺激的zif/268 mRNA。此外，依替必利部分阻断了两种苯丙胺对皮层zif/268的诱导作用。两种拮抗剂均能预防兴奋剂诱导的运动亢进和刻板行为。这些结果表明，中脑边缘/中脑纹状体通路中的D1和D2受体均调节苯丙胺和甲基苯丙胺刺激的行为及zif/268 mRNA表达。此外，发现D2受体阻断对zif/268表达的影响取决于精神兴奋剂给药后所研究的时间间隔。
