THE EFFECTS OF COCAINE ON DOPAMINE UPTAKE IN THE RAT BRAIN

可卡因对大鼠大脑多巴胺摄取的影响

基本信息

项目摘要

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.
大脑中的多巴胺能神经元被认为扮演着重要的角色 在精神分裂症的病因学上。一种关于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所致。这个 毒品可卡因增强了大脑中多巴胺的作用。人类是谁 长时间服用大剂量可卡因可能会受到伤害 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,重复的 在大鼠体内注射大剂量可卡因可以减少 在运动活动中,缺乏通常看到的敏感化状态 与较低剂量的兴奋剂挑战。在早期的研究中,我们 评价可卡因使用对多巴胺摄取的影响 在老鼠的三个大脑区域。注射可卡因(10毫克/公斤) 每天两次腹腔注射,连续七天。动物被献上了祭品 在最后一次注射和摄取~3H-多巴胺后两周 前额叶皮质、纹状体和伏隔核的突触体 检查过了。对照组动物为大鼠,注射相同剂量的 用生理盐水排定时间表。接受可卡因的动物表现出显著的 与生理盐水处理的大鼠相比,运动能力降低。 此外,这些动物对挑战剂量的运动反应 可卡因(2.5毫克/公斤和5.0毫克/公斤)或苯丙胺(1毫克/公斤)的剂量相同, 表明缺乏行为敏感度。~3H-多巴胺的摄取 可卡因处理大鼠额叶皮质突触体 与生理盐水组相比显著降低(30%), 是由于多巴胺吸收泵的Vmax降低所致。gbr 多巴胺摄取的选择性抑制剂12909和可卡因的摄入量较少 有效抑制额叶突触体内的多巴胺摄取 皮质与纹状体和伏隔核相比。类似的研究 已经对大鼠细胞体中的多巴胺摄取进行了研究 脑(腹侧被盖区和黑质)。政府当局 可卡因(10毫克/公斤×2,连续7天)对 纹状体腹侧被盖区脑片对多巴胺的摄取 或最后一次注射后一周或六周的黑质。千米 这三个大脑区域的多巴胺摄取值是相似的, 而纹状体摄取多巴胺的Vmax值为 黑质的Vmax大约是Vmax的8倍 腹侧被盖区。

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{{ truncateString('J M MASSERANO', 18)}}的其他基金

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儿茶酚胺能细胞系中多巴胺诱导的神经毒性
  • 批准号:
    5203799
  • 财政年份:
  • 资助金额:
    --
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DOPAMINE INDUCED NEUROTOXICITY IN A CATECHOLAMINERGIC CELL LINE
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  • 批准号:
    6111174
  • 财政年份:
  • 资助金额:
    --
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  • 批准号:
    3781515
  • 财政年份:
  • 资助金额:
    --
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