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 在精神分裂症的病因学中， 多巴胺在大脑某些区域的不平衡。 可卡因能增强 多巴胺在大脑中的作用 吸食可卡因的人 长期服用可能会出现长期的症状， 抑郁和冷漠类似的阴性症状， 精神分裂症 同样，在大鼠中， 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. 在本研究中，我们评估了可卡因的作用， 给药对五种脑组织中酪氨酸羟化酶活性的影响 老鼠的区域 以10 mg/kg的剂量给予考地平 腹膜内，每天两次，持续7天。 将动物 在末次注射后1小时和1、3、6和12周处死， 在前额叶中测定酪氨酸羟化酶的活性 皮质、纹状体、丘脑核、黑质和腹侧 被盖区 对照动物由注射相同药物的大鼠组成。 生理盐水的时间表 酪氨酸羟化酶活性显著升高， 可卡因处理动物的延髓核增加（11%） 和黑人（14%）在最后一次可卡因给药后1小时。 一个更 酪氨酸羟化酶活性显著增加约 术后6周和12周，50%发生在腹侧被盖区。 最后一次服用可卡因 活动没有其他变化 酪氨酸羟化酶在其他任何时间在五个大脑区域。 这些数据表明腹侧被盖区的细胞体 对慢性可卡因治疗的反应延迟， 表现为酪氨酸羟化酶活性的增加。

Dopaminergic neurons in the brain are thought to play an important role in the etiology of schizophrenia, which 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 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 activity of tyrosine hydroxylase in five brain regions of rats. Cocaine was administered in a dose of 10 mg/kg intraperitoneally, given twice a day for 7 days. The animals were sacrificed 1 hour and 1, 3, 6, and 12 weeks after the last injection and the activity of tyrosine hydroxylase was measured in the prefrontal cortex, striatum, nucleus accumbens, substantia nigra and ventral tegmental area. Control animals consisted of rats injected on the same schedule with saline. Tyrosine hydroxylase activity was significantly increased in the cocaine-treated animals in the nucleus accumbens (11%) and nigra (14%) one hour after the last cocaine administration. A more substantial increase in tyrosine hydroxylase activity of approximately 50% occurred in the ventral tegmental area at 6 and 12 weeks after the last cocaine administration. There were no other changes in the activity of tyrosine hydroxylase at any other times in the five brain regions. These data indicate that the cell bodies of the ventral tegmental area are showing a delayed response to chronic cocaine treatment as represented by the increase in tyrosine hydroxylase activity.