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。精神分裂症被认为是由于 脑部某些区域的多巴胺失衡。毒品可卡因 增强大脑中多巴胺的作用。服用可卡因的人类 长时间服用高剂量可能会出现以下症状 长期的抑郁和冷漠，类似于 精神分裂症患者。同样，反复服用大剂量的 可卡因在大鼠体内会导致运动能力下降和缺乏 小剂量刺激性药物常见的致敏状态 挑战。同样的结果也发生在动物身上 反复受到不可避免的冲击，这可能会导致无法应对， 多巴胺功能抑制和行为抑郁。我们发现 反复服用可卡因显著增加了 腹侧被盖区1、6的酪氨酸羟化酶活性 给药后12周。这一增长受到了 NMDA拮抗剂MK-801和多巴胺D2拮抗剂氟哌啶醇和 氯氮平。反复不可避免的脚步冲击导致了 酪氨酸羟基酶活性在最后一次照射后1~8天的变化 腹侧被盖区、蓝斑、皮质区和 小脑。这些增加是由于酪氨酸羟基酶的增加。 蛋白质经Western分析测定。此外，单身人士和 反复足电击增加3-甲氧基酪胺，3，4-二羟基- 苯乙酸和高香草酸在额叶皮质中的水平， 下丘脑、伏隔核和纹状体。两周后的最后一次 重复足底电击训练，大脑皮层对 反复足电击，而伏隔核和下丘脑 表现出抑制的反应。

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, 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. Similar results occur following treatment of animals with repeated inescapable shock, which can lead to a failure to cope, inhibition of dopamine function and behavioral depression. We found that repeated cocaine administration produced a significant increase in tyrosine hydroxylase activity in the ventral tegmental area at one, six and 12 weeks after administration. This increase was inhibited by the NMDA antagonist, MK-801, and the dopamine D2 antagonists, haloperidol and clozapine. Repeated inescapable footshock produced an increase in tyrosine hydroxylase activity from one to eight days after the last treatment in the ventral tegmental area, locus ceruleus, cortex and cerebellum. These increases were due to increase tyrosine hydroxylase protein as measured by Western analysis. In addition, single and repeated footshock increased 3-methoxytyramine, 3,4-dihydroxy- phenylacetic acid, and homovanillic acid levels in the frontal cortex, hypothalamus, nucleus accumbens and striatum. Two weeks after the last repeated footshock session, the cortex showed a sensitized response to the repeated footshock, whereas the nucleus accumbens and hypothalamus showed an inhibited response.