Alburges M E, Crouch D J, Andrenyak D M, Wamsley J K
Pharmacology and Toxicology Department, University of Utah, Salt Lake City 84108, USA.
Neurochem Int. 1996 Jan;28(1):51-7. doi: 10.1016/0197-0186(95)00061-c.
In previous studies, we reported time-dependent and dose-dependent changes in the rat dopaminergic receptor system following chronic administration of cocaine. The aim of the present investigation was to monitor the concentration of monoamines (using HPLC-ECD) and cocaine (using GC-PCI/MS) in rat CNS following a dose schedule of 5, 10, 15, 20 and 25 mg/kg, i.p., b.i.d. for 21 days. 12 h after the last cocaine injection, cortical and striatal concentrations of monoamines and their metabolites were not significantly different in saline vs cocaine treated animals. In addition, the cocaine concentration in the brain regions examined did not change with the different doses used. Accumulation of a metabolite of cocaine (ecgonine methyl ester) was the only alteration found. These results indicate that alterations in the dopaminergic receptor system following chronic cocaine administration are not due to changes in neurotransmitter concentration or accumulation of cocaine in the brain.
在先前的研究中,我们报道了长期给予可卡因后大鼠多巴胺能受体系统随时间和剂量的变化。本研究的目的是监测大鼠中枢神经系统中单胺类物质(采用高效液相色谱-电化学检测法)和可卡因(采用气相色谱-化学电离质谱法)的浓度,给药方案为腹腔注射,剂量分别为5、10、15、20和25mg/kg,每日两次,持续21天。在最后一次注射可卡因12小时后,生理盐水处理组和可卡因处理组动物的皮质和纹状体中单胺类物质及其代谢产物的浓度没有显著差异。此外,在所检测的脑区中,可卡因浓度并未随所用不同剂量而改变。唯一发现的变化是可卡因的一种代谢产物(芽子碱甲酯)的蓄积。这些结果表明,长期给予可卡因后多巴胺能受体系统的改变并非由于神经递质浓度的变化或大脑中可卡因的蓄积。