THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN

大脑中的多巴胺能神经元被认为在 精神分裂症的病因学一种精神分裂症的理论认为 这是由于某些大脑区域的多巴胺失衡。的 可卡因能增强多巴胺在大脑中的作用。的人类 长期服用高剂量可卡因可能会 长期抑郁和冷漠的症状类似于阴性 精神分裂症患者的症状同样，重复 在大鼠中给予高剂量的可卡因可以产生减少 在自发活动和缺乏通常的敏化状态， 低剂量兴奋剂药物的挑战。在早期的研究中，我们 评估了可卡因给药对多巴胺摄取的影响， 老鼠大脑的三个区域。给药复方甘草酸苷（10 mg/kg） 每天两次腹腔注射，持续7天。处死动物 最后一次注射后两周， 额叶皮质、纹状体和丘脑核的突触体被 考察 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，自发活动减少。 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）或安非他明（1 mg/kg）的剂量相同， 表明缺乏行为敏感性3 H-多巴胺的上升 可卡因处理大鼠额叶皮层的突触体中， 与盐水处理的大鼠相比显著降低（30%）， 是由于多巴胺摄取泵的Vmax降低。GBR 12909，多巴胺摄取的选择性抑制剂，和可卡因 有效抑制多巴胺从额叶进入突触体 皮质与纹状体和丘脑核相比。类似研究 在老鼠的细胞体中进行多巴胺摄取 大脑（腹侧被盖区和黑质）。政府当局 可卡因（10 mg/kg × 2，7天）的剂量对 纹状体腹侧被盖区脑片多巴胺摄取 或在最后一次注射后的一周或六周的黑质。的Km 这三个脑区的多巴胺摄取值相似， 而纹状体中多巴胺摄取的Vmax值为 比黑质中的Vmax高约8倍， 腹侧被盖区

Dopaminergic neurons in the brain are thought to play an important role in the etiology of schizophrenia. One theory of schizophrenia suggests that it is due to an imbalance of dopamine tn certain brain areas. 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 pro longed depression and apathy similar to the negative symptoms seen in schizophrenic patients. Similarly, the repeated administration of high doses of cocaine in rats can produce a decrease in locomotor activity and a lack of the usual sensitization state seen with lower dose stimulant drug challenges. In earlier studies, 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 seven days. The animals were sacrificed two weeks after the last injection and the up take of 3H-dopamine into synaptosomes from the frontal cortex, striatum and nucleus accumbens were 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, indicating a lack of behavioral sensitization. The up take of 3H-dopamine into synaptosomes of the frontal cortex of cocaine treated rats was significantly decreased (30%) as compared to the saline treated rats and was due to a decrease in the Vmax of the up take pump for dopamine. GBR 12909, a selective inhibitor of dopamine up take, and cocaine were less effective at inhibiting dopamine up take in synaptosomes from the frontal cortex as compared to the striatum and nucleus accumbens. Similar studies have been performed on dopamine up take in the cell bodies of the rat brain (ventral tegmental area and substantia nigra). The administration of cocaine (10 mg/kg x 2 for seven days) produced no differences in the uptake of dopamine in slices from the striatum, ventral tegmental area or substantia nigra at one or six weeks after the last injection. The Km values for dopamine up take were similar in these three brain areas, whereas the Vmax value for dopamine uptake in the striatum was approximately eight-fold higher than the Vmax in the substantia nigra and ventral tegmental area.