D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior.
D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior.
复制标题
新生多巴胺去神经大鼠纹状体黑质神经元中 D1 多巴胺受体介导的 P 物质消耗：对自伤行为的影响。
DOI：
10.1016/0006-8993(89)90305-3
复制
发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Sivam,SP
中科院分区：
文献类型：
--
作者：
Sivam,SP
本研究观察了多巴胺（DA）受体激动对6-羟基多巴胺（6-OHDA）损毁新生SD大鼠基底节脑啡肽（Met 5-enkephalin; ME）和速激肽（substance P; SP）系统的影响。已经提出，新生6-OHDA损伤大鼠可以作为在儿童神经系统疾病Lesch-Nyhan综合征中观察到的DA缺乏和自伤行为（SIB）的模型。与早期的工作一致，本研究发现，当作为成年人进行测试时，新生儿在3天龄时进行6-OHDA治疗，减少DA，并导致ME增加，纹状体和黑质中SP含量减少。对受损动物给予多巴胺前体l-二羟基苯丙氨酸（l-DOPA），诱导SIB;增加DA和DOPAC水平;纹状体和黑质中SP水平的下降幅度（−64%）大于单独损伤（−28%）。D1受体拮抗剂SCH-23390预处理可阻断多巴诱导的SP水平下降和损伤动物中观察到的SIB。此外，给予D1受体激动剂SKF-38393，而不是D2受体激动剂LY-171555，在所有方面都模拟了DOPA反应，除了激动剂不改变DA或DOPAC水平。DA激动剂或拮抗剂治疗均不影响纹状体中ME水平的损伤诱导的增加。这些结果表明，第一次，在新生儿多巴胺能去神经动物的DA受体激动剂沉淀的SIB，是与一个显着的和选择性的减少SP在纹状体黑质SP神经元。这个过程有两个组成部分：（a）由于新生儿多巴胺能去神经支配，SP系统发育迟缓;（B）剩余SP耗竭，推测是由于D1 DA受体介导的纹状体黑质SP神经元激活引起的释放增强。
The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder, Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor,l-dihydroxyphenylalanine (l-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (−64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (−28%). Thel-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1receptor antagonist, SCH-23390. Moreover, administration of the D1receptor agonist, SKF-38393, but not the D2agonist, LY-171555, to lesioned animals mimicked thel-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation; and (b) a depletion of the remaining SP, presumably by enhanced release due to D1DA receptor-mediated activation of striatonigral SP neurons.