DIFFERENTIAL DOPAMINERGIC REGULATION OF THE NEUROTENSIN STRIATONIGRAL AND STRIATOPALLIDAL PATHWAYS IN THE RAT

DIFFERENTIAL DOPAMINERGIC REGULATION OF THE NEUROTENSIN STRIATONIGRAL AND STRIATOPALLIDAL PATHWAYS IN THE RAT
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DOI:
10.1016/0014-2999(94)90021-3
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发表时间:
1994-09-01
影响因子:
5
通讯作者:
HOKFELT, T
HOKFELT, T
中科院分区:
医学2区
文献类型:
--
作者:
CASTEL, MN;MORINO, P;HOKFELT, T

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最近,一种被甲基苯丙胺强烈上调的神经紧张素纹状核通路的存在被证实。本研究的目的是利用免疫组织化学和放射免疫分析法来研究多巴胺拮抗剂对这一途径的调节。大鼠分别注射甲基苯丙胺或与多巴胺D-1受体拮抗剂SCH 23390 (R(+)-7-氯-8-羟基-3-甲基-1-苯基-2 h -3-苯甲平盐酸)或多巴胺D-2受体拮抗剂舒匹利。两种技术都表明,这种神经紧张素纹状体通路是由多巴胺D-1受体调节的,因为SCH 23390完全阻止了甲基苯丙胺诱导的纹状体和网状黑质神经紧张素样免疫反应性的增加。相反,舒必利不能抵消甲基苯丙胺在这两个区域的作用,这表明多巴胺D-2受体不参与这一神经紧张素途径的调节。另一方面,舒匹利治疗后纹状体细胞体和苍白球的神经紧张素样免疫反应性明显增强,表明该途径主要受多巴胺D-2受体调节。
Recently the existence of a neurotensin striatonigral pathway strongly up-regulated by methamphetamine has been demonstrated. The aim of the present study was to investigate, using immunohistochemistry and radioimmunoassay, the modulation of this pathway by dopamine antagonists. Rats were injected either with methamphetamine alone or together with the dopamine D-1 receptor antagonist, SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2 H-3-benzapine hydrochloride), or with the dopamine D-2 receptor antagonist, sulpiride. Both techniques showed that this neurotensin striatonigral pathway is regulated by dopamine D-1 receptors, since SCH 23390 totally prevented the methamphetamine-induced increase in neurotensin-like immunoreactivity, both in the striatum and in the substantia nigra pars reticulata. Conversely, sulpiride was unable to counteract the effect of methamphetamine in these two areas, suggesting that dopamine D-2 receptors are not involved in the regulation of this neurotensin pathway. On the other hand, neurotensin-like immunoreactivity was markedly increased in striatal cell bodies and in the globus pallidus after treatment with sulpiride, indicating that this pathway is mainly regulated by dopamine D-2 receptors.