THE EFFECTS OF COCAINE ON TYROSINE HYDROXYLASE ACTIVITY IN THE RAT BRAIN

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，缺乏通常所见的敏感化状态 用较低剂量的兴奋剂进行挑战。在早期的研究中，我们 评价可卡因给药对大鼠脑内神经细胞活性的影响 大鼠五个脑区的酪氨酸羟基酶。注射可卡因 剂量为10 mg/kg，每天两次，共7次 几天后，酪氨酸羟基酶活性显著增加 在6岁和12岁时腹侧被盖区约50% 在最后一次注射可卡因几周后。类似的研究已经被 测量这些脑组织中酪氨酸的体内羟化 地区。可卡因使酪氨酸显著减少。 额叶皮质(30%)和伏隔核(34%)的羟化 与最后一次注射六周后注射生理盐水的大鼠相比， 两周后没有显著差异，这些数据表明 可卡因增加腹侧被盖酪氨酸羟基酶活性 额叶皮质对多巴胺合成减少的反应区域 和伏隔核。最近，我们已经开始了一些研究，以测量 人脑组织中酪氨酸羟基酶的活性。酪氨酸 可以检测到人体皮质组织中的羟基酶活性 使用浓缩器-过滤系统(Centricon、Amcon)。不过，这个 活动量相对较低(两次空白)，其他研究正在进行中 提高检测灵敏度的研究进展。

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 in 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 challenge. In earlier studies, we evaluated the effects of cocaine administration on the activity of tyrosine hydroxylase in five brain regions of rats. Cocaine, administered in a dose of 10 mg/kg intraperitoneally, given twice a day for seven days, produced a significant increase in tyrosine hydroxylase activity of approximately 50% in the ventral tegmental area at six and twelve weeks after the last cocaine administration. Similar studies have been performed measuring the in vivo hydroxylation of tyrosine in these brain regions. Cocaine produced a significant decrease in tyrosine hydroxylation in the frontal cortex (30%) and nucleus accumbens (34%) compared with saline treated rats six weeks after the last injection, with no significant differences after two week& These data suggest that cocaine increases tyrosine hydroxylase activity in the ventral tegmental area in response to decreased synthesis of dopamine in the frontal cortex and nucleus accumbens. Recently, we have initiated studies to measure tyrosine hydroxylase activity in human brain tissue. Tyrosine hydroxylase activity can be detected in human cortical tissue with the use of concentrator-filtration system (Centricon, Amicon). However, this activity is relatively low (twice blank) and additional studies are in progress to enhance the sensitivity of the assay.