THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN

可卡因能增强多巴胺在大脑中的作用。 人类 长期服用高剂量可卡因的人 长期抑郁和冷漠的症状类似于阴性 精神分裂症的症状 同样，在大鼠中， 服用高剂量的可卡因可以减少 自发活动和缺乏常见的致敏状态， 低剂量兴奋剂药物挑战。 在本研究中，我们评估了 可卡因给药对三个人多巴胺摄取的影响 老鼠的大脑区域。 给药复方甘草酸苷（10 mg/kg） 腹腔内注射，每天两次，持续7天。 处死动物 在最后一次注射后两周， 前额叶皮层、纹状体和丘脑核的突触体 进行了检查。 对照动物由注射相同药物的大鼠组成。 生理盐水的时间表 接受可卡因的动物表现出显著的 与盐水处理的大鼠相比，运动活动减少。 此外，这些动物对激发剂量的运动反应 可卡因（2.5和5.0 mg/kg）或苯丙胺（1 mg/kg）的剂量相同。 大鼠前额叶皮层突触体对~ 3 H-多巴胺的摄取 可卡因处理的大鼠与对照组相比显著降低（30%）， 盐水处理的大鼠。 这些之间没有显著差异 各组大鼠纹状体或中脑核多巴胺摄取。 对数据的动力学分析表明多巴胺的减少 可卡因治疗大鼠的前额皮质的摄取是由于 多巴胺摄取泵的Vmax降低。GBR 12909，a 选择性多巴胺摄取抑制剂，可卡因抑制3 H-多巴胺 前额叶皮层、纹状体和丘脑核的吸收， 类似的方式。 用甲基苯丙胺治疗大鼠，使用相同的 范式，并没有产生任何变化，多巴胺摄取在三个 大脑区域，表明可卡因在产生 前额叶皮层多巴胺摄取量减少

The drug cocaine enhances the action of dopamine in the brain. Humans who take cocaine in high doses for a prolonged period of time may suffer symptoms of prolonged depression and apathy similar to the negative symptoms seen in schizophrenics. Similarly, in rats, the chronic administration of high doses of cocaine can produce a decrease in locomotor activity and a lack of the usual sensitization state seen with lower dose stimulant drug challenge. In the present study, we evaluated the effects of cocaine administration on the uptake of dopamine in three brain areas of the rat. Cocaine (10 mg/kg) was administered intraperitoneally twice a day for 7 days. The animals were sacrificed two weeks after the last injection, and the uptake of 3H-dopamine into synaptosomes from the prefrontal cortex, striatum and nucleus accumbens was examined. Control animals consisted of rats injected on the same schedule with saline. Animals receiving cocaine exhibited a significant decrease in locomotor activity as compared to the saline-treated rats. In addition, the locomotor responses of these animals to a challenge dose of cocaine (2.5 and 5.0 mg/kg) or amphetamine (1 mg/kg) were the same. The uptake of 3H-dopamine into synaptosomes of the prefrontal cortex of cocaine-treated rats was significantly decreased (30%) as compared to the saline-treated rats. There were no significant differences between these groups of rats in dopamine uptake in the striatum or nucleus accumbens. Kinetic analysis of the data indicated that the decrease in dopamine uptake in the prefrontal cortex of the cocaine-treated rats was due to a decrease in the Vmax of the uptake pump for dopamine. GBR12909, a selective inhibitor of dopamine uptake, and cocaine inhibited 3H-dopamine uptake into the prefrontal cortex, striatum and nucleus accumbens in a similar manner. Treatment of rats with methamphetamine, using the same paradigm, did not produce any changes in dopamine uptake in the three brain areas, indicating that cocaine was selective in producing the decrease in dopamine uptake in the prefrontal cortex.