Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats.
Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats.
复制标题
个体发生喹吡罗治疗未能引发 D2 激动剂增强 6-羟基多巴胺损伤大鼠的运动活性。
DOI：
10.1007/bf03033153
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发表时间：
2003
影响因子：
3.7
通讯作者：
Kostrzewa,JohnP
中科院分区：
文献类型：
--
作者：
Brus,Ryszard;Kostrzewa,RichardM;Nowak,Przemysław;Perry,KenW;Kostrzewa,JohnP
用多巴胺(DA)D2受体激动剂重复治疗会导致DA D2受体超敏反应的诱导，对随后的D2受体激动剂治疗的行为反应增强就是证据--这种现象被称为受体刺激。D2受体的启动已经在正常(非损毁)大鼠中得到了很好的研究。与D2启动相反，重复使用DA D1激动剂不能激活D1受体，除非黑质纹状体DA纤维在出生后早期个体发育中大部分被破坏。为了确定在出生后早期黑质纹状体DA纤维被大量破坏的大鼠是否可以启动D2受体，我们(A)在出生后3天用6-羟基多巴胺(每侧脑室67μg；地昔帕明，20 mg/kg ip，1 h；6-羟基多巴胺，20 mg/kg ip，1 h；6-羟基多巴胺)损毁大鼠，(B)出生后前28天每天用D2激动剂盐酸奎比罗(3.0 mg/kg ip)治疗，(C)观察到奎比罗诱导的和SKF 38393-(DA1激动剂)诱导的成年期运动活动和刻板行为。在内源性纹状体DA减少99%的6-OHDA损毁大鼠中，奎比罗不能产生增强的运动或刻板的活动。然而，SKF 38393即使在第一剂SKF 38393之后也能产生更多的运动和刻板印象的活动。这些发现表明，在6-OHDA损伤的新生大鼠中，虽然D2激动剂治疗至少部分地激活了D1受体，但个体发育的奎匹罗治疗并没有启动D2受体。
Repeated treatments with a dopamine (DA) D2receptor agonist result in the induction of DA D2receptor supersensitivity, as evidenced by enhanced behavioral responses to subsequent D2agonist treatments—a phenomenon known asprimingof receptors. Priming of D2receptors has been well-studied in otherwise intact (non-lesioned) rats. In contrast to D2priming, repeated treatments with a DA D1agonist are unable to prime D1receptors unless nigrostriatal DA fibers are largely destroyed in early postnatal ontogeny. In order to determine if D2receptors could be primed in rats in which nigrostriatal DA fibers were largely destroyed in early postnatal ontogeny, rats were (a) lesioned at 3 days after birth with 6-hydroxydopamine (67 μg in each lateral ventricle; desipramine, 20 mg/kg IP, 1 h; 6-OHDA), (b) treated daily for the first 28 days after birth with the D2agonist quinpirole HCl (3.0 mg/kg IP), and (c) observed in adulthood for both quinpirole-induced and SKF 38393- (D1agonist-) induced locomotor activity and stereotyped activities. In 6-OHDA-lesioned rats in which endogenous striatal DA was reduced by 99%, quinpirole did not produce enhanced locomotor or stereotyped activities. However, SKF 38393 produced increased locomotor and stereotyped activities even after the first dose of SKF 38393. These findings demonstrate that D2receptors are not primed by ontogenetic quinpirole treatments of neonatally 6-OHDA-lesioned rats, although D2agonist treatments do at least partially prime D1receptors in 6-OHDA-lesioned rats.