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在 精神分裂症的病因学 精神分裂症被认为是由于 大脑某些区域的多巴胺失衡 毒品可卡因 增强多巴胺在大脑中的作用。 吸食可卡因的人 在高剂量的一段较长的时间可能会遭受的症状， 长期的抑郁和冷漠类似的阴性症状， 精神分裂症 类似地，在大鼠中，重复给予高剂量的 剂量的可卡因可导致自发活动减少， 低剂量兴奋剂药物常见的致敏状态 挑战. 在早期的研究中，我们评估了可卡因对 大鼠五个脑区酪氨酸羟化酶的活性。 以10 mg/kg的剂量腹膜内给予考地平，给药两次 连续7天， 腹侧被盖区的羟化酶活性约为50% 分别在最后一次服用可卡因后的第6周和第12周。 类似 已经进行了测量以下物质的体内羟基化的研究 这些脑区的酪氨酸。 成本大幅下降 在额叶皮质（30%）和核酪氨酸羟化 与生理盐水处理的大鼠相比， 最后一针 可卡因诱导的酪氨酸羟化酶升高 腹侧被盖区的活动被NMDA阻止 拮抗剂MK-801和多巴胺D2拮抗剂氟哌啶醇和 氯氮平 D_1受体拮抗剂SCH 23390与对照组相比， 对酪氨酸羟化酶活性增加的影响，以及SCH 23390 单独增强酪氨酸羟化酶活性。

Dopaminergic neurons in the brain are thought to play an important role in the etiology of schizophrenia. Schizophrenia is thought to be 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 prolonged depression and apathy similar to the negative symptoms seen in schizophrenics. Similarly, in rats the repeated 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 earlier studies, we evaluated the effects of cocaine 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 12 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. The cocaine-induced increase in tyrosine hydroxylase activity in the ventral tegmental area was prevented by the NMDA antagonist, MK-801, and the dopamine D2 antagonists, haloperidol and clozapine. The D1 receptor antagonist, SCH23390 had no significant effect on the increase in tyrosine hydroxylase activity, and SCH23390 alone enhanced tyrosine hydroxylase activity.