Brus Ryszard, Kostrzewa Richard M, Nowak Przemysław, Perry Ken W, Kostrzewa John P
Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland.
Neurotox Res. 2003;5(5):329-38. doi: 10.1007/BF03033153.
Repeated treatments with a dopamine (DA) D2 receptor agonist results in the induction of DA D2 receptor supersensitivity, as evidenced by enhanced behavioral responses to subsequent D2 agonist treatments - a phenomenon known as priming of receptors. Priming of D2 receptors has been well-studied in otherwise intact (non-lesioned) rats. In contrast to D2 priming, repeated treatments with a DA D1 agonist are unable to prime D1 receptors unless nigrostriatal DA fibers are largely destroyed in early postnatal ontogeny. In order to determine if D2 receptors 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 micrograms 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 D2 agonist quinpirole HCl (3.0 mg/kg IP), and (c) observed in adulthood for both quinpirole-induced and SKF 38393- (D1 agonist-) 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 D2 receptors are not primed by ontogenetic quinpirole treatments of neonatally 6-OHDA-lesioned rats, although D2 agonist treatments do at least partially prime D1 receptors in the 6-OHDA-lesioned rats.
用多巴胺（DA）D2受体激动剂反复治疗会导致DA D2受体超敏反应的诱导，这表现为对后续D2激动剂治疗的行为反应增强——这一现象被称为受体致敏。D2受体致敏在其他方面完好无损（未损伤）的大鼠中已得到充分研究。与D2致敏相反，用DA D1激动剂反复治疗无法使D1受体致敏，除非在出生后早期发育阶段黑质纹状体DA纤维被大量破坏。为了确定在出生后早期发育阶段黑质纹状体DA纤维被大量破坏的大鼠中D2受体是否能被致敏，将大鼠：（a）在出生后3天用6-羟基多巴胺（每侧脑室67微克；去甲丙咪嗪，20毫克/千克腹腔注射，1小时；6-OHDA）进行损伤；（b）在出生后的前28天每天用D2激动剂盐酸喹吡罗（3.0毫克/千克腹腔注射）进行治疗；（c）在成年期观察喹吡罗诱导的和SKF 38393（D1激动剂）诱导的运动活动和刻板行为。在6-OHDA损伤的大鼠中，内源性纹状体DA减少了99%，喹吡罗并未产生增强的运动或刻板行为。然而，即使在首次给予SKF 38393后，SKF 38393也产生了增加的运动和刻板行为。这些发现表明，出生时6-OHDA损伤的大鼠在发育过程中接受喹吡罗治疗不会使D2受体致敏，尽管D2激动剂治疗至少能部分使6-OHDA损伤大鼠中的D1受体致敏。
