Effect of raclopride on dopamine D2 receptor mRNA expression in rat brain.
Effect of raclopride on dopamine D2 receptor mRNA expression in rat brain.
复制标题
雷氯必利对大鼠脑内多巴胺 D2 受体 mRNA 表达的影响。
DOI：
10.1016/0306-4522(92)90028-z
复制
发表时间：
1992
期刊：
影响因子：
3.3
通讯作者：
Sedvall,G
中科院分区：
文献类型：
--
作者：
Kopp,J;Lindefors,N;Brené,S;Hall,H;Persson,H;Sedvall,G
已知多巴胺D2受体拮抗剂的长期治疗可提高大鼠和人脑中尾壳核和中脑核中多巴胺D2受体结合位点的密度。本研究采用多巴胺D2受体拮抗剂雷氯必利（3 μmol/kg，s.c.）用原位杂交法测定单次注射或每日给药18天是否改变了大鼠尾壳核和海马多巴胺D2受体mRNA的表达。单次注射雷氯必利并没有显著改变多巴胺D2受体mRNA表达神经元在任何区域的数量密度。每天给予雷氯必利18天，导致背外侧尾壳核中表达可检测量多巴胺D2受体mRNA的细胞数量增加31%，并且在乳胶浸渍载玻片上测量的该脑区中单个杂交阳性神经元的银颗粒面积增加20%。D2受体mRNA水平在背外侧尾壳核的区域特异性增加，证实了通过测量X射线胶片放射自显影杂交信号。处理18天后，内侧尾壳核和延髓D2受体mRNA水平无明显变化。背外侧尾壳核多巴胺D2受体mRNA表达的区域选择性增加表明这种神经抑制剂对尾壳核神经元亚群中多巴胺D2受体mRNA表达的差异性调节，我们认为，已知尾壳核中多巴胺D2受体密度的增加在一定程度上是在基因表达水平上受到调节的。
Prolonged treatment with dopamine D2receptor antagonists is known to elevate the density of dopamine D2receptor binding sites in caudate-putamen and nucleus accumbens in rat and human brain. In this study we used the dopamine D2receptor antagonist raclopride (3 μmol/kg, s.c.) to determine if a single injection or daily administration of this drug for up to 18 days changed the expression of dopamine D2receptor mRNA in rat caudate-putamen and accumbens as measured byin situhybridization. A single injection of raclopride did not significantly change the numerical density of dopamine D2receptor mRNA-expressing neurons in any of the regions examined. A daily administration of raclopride for 18 days resulted in a 31% increase in the number of cells expressing detectable amounts of dopamine D2receptor mRNA in dorsolateral caudate-putamen and in a 20% increase in the area of silver grains over individual hybridization-positive neurons in this brain region measured on emulsiondipped slides. The region-specific increase in the D2receptor mRNA level in dorsolateral caudate-putamen was confirmed by measurement of the hybridization signal on X-ray film autoradiograms. The levels of D2receptor mRNA remained unchanged in medial caudate-putamen and accumbens after 18 days' treatment. The region-selective increase in dopamine D2receptor mRNA expression in dorsolateral caudate-putamen indicates a differential regulation of dopamine D2receptor mRNA expression in a subpopulation of caudate-putamen neurons by this neuroleptic.We suggest that the increase in dopamine D2receptor density in caudate-putamen known to follow prolonged dopamine D2receptor blockade to some extent is regulated at the level of gene expression.