Angulo J A, Coirini H, Ledoux M, Schumacher M
Rockefeller University, Laboratory of Neuroendocrinology, New York, NY 10021.
Brain Res Mol Brain Res. 1991 Sep;11(2):161-6. doi: 10.1016/0169-328x(91)90117-g.
The effect of dopamine depletion or pharmacological blockade of dopamine receptors on striatal and accumbens dopamine D2 mRNA and receptor levels was assessed by in situ hybridization histochemistry and receptor autoradiography. The time course of pharmacological blockade with haloperidol demonstrates a complex mode of regulation of dopamine D2 mRNA and receptor levels. By day 8 of haloperidol treatment, D2 mRNA and receptor levels were decreased (up to 20%) in the medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). However, by day 21 of haloperidol treatment, D2 mRNA and receptor were increased relative to vehicle-injected controls. Likewise, unilateral dopamine depletion due to 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neurons resulted in decreased levels of D2 receptor mRNA by day 8 post-lesion in the ipsilateral mCPU, aCPU and the NAc. However, at days 14 or 21 post-lesion, there was a reversal of the effect with increases of up to 22% in all brain regions ipsilateral to the lesion. Although no decreases in receptor level were observed at day 8, significant increases in receptor level in all three brain regions were detected at days 14 and 21 post-lesion. The results demonstrate that midbrain dopaminergic innervation exerts tonic effects on the levels of dopamine D2 receptor and mRNA in the caudate-putamen and the nucleus accumbens of the rat. Changes in receptor level are frequently accompanied by comparable changes in mRNA level, indicating a mass action relationship between receptor level and receptor biosynthesis in these forebrain regions in the rat.
通过原位杂交组织化学和受体放射自显影技术，评估了多巴胺耗竭或多巴胺受体的药理学阻断对纹状体和伏隔核中多巴胺D2 mRNA及受体水平的影响。氟哌啶醇药理学阻断的时间进程显示出多巴胺D2 mRNA和受体水平的复杂调节模式。在氟哌啶醇治疗的第8天，尾状核-壳核（mCPU和aCPU）及伏隔核（NAc）的内侧和前部区域中，D2 mRNA和受体水平降低（高达20%）。然而，在氟哌啶醇治疗的第21天，相对于注射溶媒的对照组，D2 mRNA和受体有所增加。同样，由于中脑多巴胺能神经元的6-羟基多巴胺（6-OHDA）损伤导致的单侧多巴胺耗竭，在损伤后第8天，同侧mCPU、aCPU和NAc中的D2受体mRNA水平降低。然而，在损伤后第14天或21天，这种效应发生了逆转，损伤同侧的所有脑区中增加了高达22%。虽然在第8天未观察到受体水平降低，但在损伤后第14天和21天，在所有三个脑区均检测到受体水平显著增加。结果表明，中脑多巴胺能神经支配对大鼠尾状核-壳核和伏隔核中多巴胺D2受体及mRNA水平具有紧张性作用。受体水平的变化常常伴随着mRNA水平的相应变化，表明在大鼠这些前脑区域中，受体水平与受体生物合成之间存在质量作用关系。
