Tsukada H, Kreuter J, Maggos C E, Unterwald E M, Kakiuchi T, Nishiyama S, Futatsubashi M, Kreek M J
Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan.
J Neurosci. 1996 Dec 1;16(23):7670-7. doi: 10.1523/JNEUROSCI.16-23-07670.1996.
The aim of the present study was to determine the effect of "binge" pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain. Male Sprague Dawley rats were injected three times at 1 hr intervals with saline or cocaine (15 mg/kg) each day for 2, 7, or 14 d. The in vivo binding of [11C]SCH23390 (dopamine D1 receptor antagonist) and [11C]N-methylspiperone (NMSP; dopamine D2 receptor antagonist) in the striatal region was measured by a high-resolution positron emission tomography at 1 and 3.5 hr, respectively, after the last cocaine or saline injection. Acute (2 d) binge cocaine administration did not change the in vivo binding potential of [11C]SCH23390 or the binding of [11C]NMSP in the striatum. After 7 d of binge cocaine administration, a significant decrease in the binding potential of [11C]SCH23390 was observed, whereas no change in the binding of [11C]NMSP was found. After 14 d of binge cocaine administration, the in vivo binding was significantly reduced for both [11C]SCH23390 and [11C]NMSP. Separate saturation experiments indicated that the observed alterations of in vivo binding were attributable mainly to apparent alterations in the affinity and not the number of binding sites. These results suggest that both dopamine D1 and D2 receptors may have altered physiologically available binding sites after binge pattern cocaine administration.
本研究的目的是确定“暴饮暴食”模式给予可卡因对大鼠脑内多巴胺D1和D2受体的影响。雄性斯普拉格-道利大鼠每天间隔1小时注射生理盐水或可卡因(15毫克/千克),共注射3次,持续2、7或14天。在最后一次注射可卡因或生理盐水后1小时和3.5小时,分别通过高分辨率正电子发射断层扫描测量纹状体区域内[11C]SCH23390(多巴胺D1受体拮抗剂)和[11C]N-甲基螺哌隆(NMSP;多巴胺D2受体拮抗剂)的体内结合情况。急性(2天)暴饮暴食式给予可卡因并未改变[11C]SCH23390的体内结合潜能或纹状体内[11C]NMSP的结合情况。暴饮暴食式给予可卡因7天后,观察到[11C]SCH23390的结合潜能显著降低,而[11C]NMSP的结合未发现变化。暴饮暴食式给予可卡因14天后,[11C]SCH23390和[11C]NMSP的体内结合均显著降低。单独的饱和实验表明,观察到的体内结合变化主要归因于亲和力的明显改变,而非结合位点数量的改变。这些结果表明,暴饮暴食式给予可卡因后,多巴胺D1和D2受体的生理可用结合位点可能均发生了改变。