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，这被认为是由于 脑部某些区域的多巴胺失衡。可卡因这种药物可以增强 多巴胺在大脑中的作用。高吸食可卡因的人 长时间服用可能会出现延长的症状 抑郁和冷漠，类似于 精神分裂症患者。同样，在大鼠中，长期服用高剂量的 剂量的可卡因会导致运动活动减少和缺乏 小剂量刺激性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效果。 给药对五种脑组织酪氨酸羟化酶活性的影响 老鼠的区域。可卡因的剂量为10毫克/公斤 腹腔注射，每日两次，连用7天。这些动物是 在最后一次注射后1小时、1周、3周、6周和12周处死动物 测定前额叶酪氨酸羟基酶活性。 皮质、纹状体、伏隔核、黑质和腹侧 被盖区。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。酪氨酸羟基酶活性显著 可卡因处理的动物伏隔核内神经元数量增加(11%) 和黑质(14%)在最后一次注射可卡因后一小时。A更多 酪氨酸羟基酶活性大幅提高约 50%发生在术后6周和12周的腹侧被盖区 最后一次注射可卡因。活动中没有其他变化。 在五个大脑区域的任何其他时间的酪氨酸羟基酶。 这些数据表明，腹侧被盖区的胞体 对慢性可卡因治疗表现出延迟反应 表现为酪氨酸羟基酶活性的增加。

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.