Zhang Yong, Schlussman Stefan D, Ho Ann, Kreek Mary Jeanne
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10021, USA.
Synapse. 2003 Dec 1;50(3):191-9. doi: 10.1002/syn.10251.
In vivo microdialysis was used to measure the effect of chronic "binge" pattern cocaine administration on basal and cocaine-induced dopamine levels in the caudate putamen and nucleus accumbens of C57BL/6J and 129/J mice. Mice were implanted with a guide cannula in the caudate putamen or nucleus accumbens and after 4 days recovery, one group received "binge" pattern cocaine administration for 13 days (15 mg/kg x 3, i.p. at hourly intervals) while another group received saline in the same pattern. On the day before microdialysis, dialysis probes were lowered into the caudate putamen and nucleus accumbens. The next morning, after baseline dopamine collection, all animals received "binge" cocaine administration. Dialysates were collected every 20 min and dopamine content was determined by HPLC with electrochemical detection. In the basal condition, the mean level of dopamine in the dialysate from both brain regions of mice pretreated with "binge" pattern cocaine administration was significantly lower than that of the mice pretreated with saline administration. The absolute levels of dopamine achieved following "binge" pattern cocaine challenge were lower in the mice that had received chronic cocaine administration. However, when expressed as percent increase over baseline, the dopamine response to cocaine in the nucleus accumbens was significantly higher in mice that received chronic than in mice that received acute cocaine administration. Chronic cocaine administration led to a lowering of both basal dopamine and the absolute levels of cocaine-induced increases of dopamine in the two brain regions, but enhanced the percent increases over the baseline in response to cocaine in the nucleus accumbens of both mouse strains.
采用体内微透析技术，测量慢性“暴饮暴食”模式给予可卡因对C57BL/6J和129/J小鼠尾壳核及伏隔核中基础多巴胺水平和可卡因诱导的多巴胺水平的影响。在小鼠的尾壳核或伏隔核植入引导套管，恢复4天后，一组小鼠接受“暴饮暴食”模式的可卡因给药13天（15mg/kg×3次，腹腔注射，每小时1次），另一组小鼠以相同模式给予生理盐水。在微透析前一天，将透析探针插入尾壳核和伏隔核。次日早晨，在收集基础多巴胺后，所有动物均接受“暴饮暴食”模式的可卡因给药。每20分钟收集一次透析液，采用高效液相色谱电化学检测法测定多巴胺含量。在基础状态下，经“暴饮暴食”模式可卡因预处理的小鼠两个脑区透析液中的多巴胺平均水平显著低于经生理盐水预处理的小鼠。接受慢性可卡因给药的小鼠在“暴饮暴食”模式可卡因激发后达到的多巴胺绝对水平较低。然而，以相对于基线的百分比增加来表示时，接受慢性给药的小鼠伏隔核中对可卡因的多巴胺反应显著高于接受急性可卡因给药的小鼠。慢性可卡因给药导致两个脑区的基础多巴胺水平以及可卡因诱导的多巴胺增加的绝对水平均降低，但增强了两种品系小鼠伏隔核中对可卡因反应相对于基线的百分比增加。
