Lim D K, Yu Z J, Hoskins B, Rockhold R W, Ho I K
Department of Pharmacology and Toxicology University of Mississippi Medical Center Jackson 39216.
Neurochem Res. 1990 Jun;15(6):629-34. doi: 10.1007/BF00973754.
The characteristics of dopamine uptake after acute and subacute cocaine administration were determined in striata from WKY and SHR. In acutely-treated (40 mg/kg, s.c.) rats, significant increases in the Vmax of dopamine uptake were observed 30 min after the cocaine injection in both strains, without changes in Km values. The in vitro IC50 for cocaine was significantly decreased at 30 min in WKY and at 2 h in SHR. However, the in vitro IC50 for GBR-12909 was significantly increased at 30 min and at 2 h in both strains following cocaine administration. In both strains, the density (Bmax) of the [3H]GBR-12935 binding site was significantly increased at 30 min and at 2 h with no changes in Kd. In subacutely-treated (20 mg/kg, twice daily for 3 or 7 days) rats, a significant increase in the Km for dopamine uptake was observed in 7 day treated SHR. The in vitro IC50 for GBR-12909 was significantly increased in 3 day treated WKY. The results suggest that cocaine administration alters dopamine uptake and characteristics of dopamine uptake sites in the rat brain.
在WKY和SHR大鼠的纹状体中测定了急性和亚急性给予可卡因后多巴胺摄取的特征。在急性给药（40mg/kg，皮下注射）的大鼠中，两种品系在注射可卡因后30分钟均观察到多巴胺摄取的Vmax显著增加，而Km值无变化。WKY大鼠在30分钟时以及SHR大鼠在2小时时，可卡因的体外IC50显著降低。然而，给予可卡因后，两种品系在30分钟和2小时时GBR-12909的体外IC50均显著增加。在两种品系中，[3H]GBR-12935结合位点的密度（Bmax）在30分钟和2小时时均显著增加，而Kd无变化。在亚急性给药（20mg/kg，每日两次，共3天或7天）的大鼠中，7天给药的SHR大鼠多巴胺摄取的Km显著增加。3天给药的WKY大鼠GBR-12909的体外IC50显著增加。结果表明，给予可卡因会改变大鼠脑中多巴胺的摄取及多巴胺摄取位点的特征。
