Differential regional effects of methamphetamine on the activities of tryptophan and tyrosine hydroxylase
Differential regional effects of methamphetamine on the activities of tryptophan and tyrosine hydroxylase
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DOI：
10.1046/j.1471-4159.1999.0720661.x
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发表时间：
1999-02-01
影响因子：
4.7
通讯作者：
Hanson, GR
中科院分区：
文献类型：
--
作者：
Haughey, HM;Fleckenstein, AE;Hanson, GR
管理高剂量的甲基苯丙胺（METH）产生短期和长期的酶缺陷在中央单胺能系统。为了确定METH治疗的这些急性和长期后果之间是否存在相关关系，在本研究中，我们检查了METH对尾状核、丘脑核和苍白球的各个区域中的色氨酸羟化酶（TPH）和酪氨酸羟化酶（TH）活性的区域效应。单次METH给药降低了苍白球中治疗后1小时的TPH活性，在前尾状核中，腹内侧比背外侧区域受影响更大。相比之下，TH活性没有减少后，无论是在尾状核或苍白球单次METH管理，但是，它被改变在丘脑核。多次METH给药后7天，TH和TPH活动在大多数尾状核区域下降，但在丘脑核或苍白球没有下降。这些数据表明：（1）METH对TPH和TH的影响存在区域差异;（2）尾状核和苍白球中TPH对METH的短期和长期区域反应相关。相比之下，甲基苯丙胺诱导的急性TH反应并不能预测TH活性的长期变化。
Administration of high doses of methamphetamine (METH) produces both short- and long-term enzymatic deficits in central monoaminergic systems. To determine whether a correlative relationship exists between these acute and long-term consequences of METH treatment, in the present study we examined the regional effects of METH on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities in Various regions of the caudate nucleus, nucleus accumbens, and globus pallidus, A single METH administration decreased TPH activity 1 h after treatment in the globus pallidus, in the nucleus accumbens, and throughout the caudate; in the anterior caudate, the ventral-medial was more affected than the dorsal-lateral region. In contrast, TH activity was not decreased in either the caudate or the globus pallidus after a single METH administration; however, it was altered in the nucleus accumbens. Seven days after multiple METH administrations, TH and TPH activities were decreased in most caudate regions but not in the nucleus accumbens or globus pallidus. These data demonstrate that (1) the effects of METH on TPH and TH vary regionally; and (2) the short-term and long-term regional responses of TPH to METH in the caudate and globus pallidus correlated. In contrast, METH-induced acute TH responses did not predict the long-term changes in TH activity.