Jiang H K, McGinty J F, Hong J S
Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
Brain Res. 1990 Jan 15;507(1):57-64. doi: 10.1016/0006-8993(90)90522-d.
Previous studies indicate that dopaminergic transmission inhibits the biosynthesis of enkephalin and stimulates that of dynorphin in the striatonigral pathway of intact rat. The purpose of this study was to determine which dopamine (DA) receptor subtype(s) mediate the modulatory actions of DA. We measured striatal and nigral levels of enkephalin and dynorphin in: (1) intact rats repeatedly injected with D1 (SKF-38393, 5 mg/kg, i.p.) or D2 (LY-171555, 1 mg/kg, i.p.) agonists, alone or in combination, (2) 6-hydroxydopamine (6-OHDA)-lesioned rats repeatedly injected with the same D1 or D2 agonists, and (3) intact rats repeatedly injected with D1 (SCH-23390, 0.05 mg/kg, s.c.) or D2 (sulpiride, 100 mg/kg, s.c.) antagonists, given alone or in combination with the mixed D1/D2 agonist apomorphine (5 mg/kg, i.p.). Repeated injections of the D1 agonist to intact rats (twice daily for 7 days) produced a small but not statistically significant increase in striatal levels of dynorphin; similar treatment with the D2 agonist did not affect dynorphin levels at all. Combined treatments with D1 and D2 agonists did not potentiate the effect of the D1 agonist. 6-OHDA lesions of the nigrostriatal DA pathway alone decreased the level of dynorphin in both the striatum and substantia nigra. However, repeated D1 agonist, but not D2, injections not only reversed the decrease in dynorphin levels, but caused a significant increase above control levels. In intact rats, repeated injections of the D1 or D2 antagonist alone failed to alter the levels of dynorphin, but the D1 antagonist, not the D2 antagonist, attenuated the apomorphine-induced increase in striatal dynorphin.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，在完整大鼠的纹状体黑质通路中，多巴胺能传递抑制脑啡肽的生物合成并刺激强啡肽的生物合成。本研究的目的是确定哪种多巴胺（DA）受体亚型介导DA的调节作用。我们在以下实验中测量了纹状体和黑质中脑啡肽和强啡肽的水平：（1）单独或联合反复注射D1（SKF-38393，5mg/kg，腹腔注射）或D2（LY-171555，1mg/kg，腹腔注射）激动剂的完整大鼠；（2）反复注射相同D1或D2激动剂的6-羟基多巴胺（6-OHDA）损伤大鼠；（3）单独或与混合D1/D2激动剂阿扑吗啡（5mg/kg，腹腔注射）联合反复注射D1（SCH-23390，0.05mg/kg皮下注射）或D2（舒必利，100mg/kg皮下注射）拮抗剂的完整大鼠。向完整大鼠反复注射D1激动剂（每日两次，共7天）使纹状体中强啡肽水平有小幅升高，但无统计学意义；用D2激动剂进行类似处理对强啡肽水平完全没有影响。D1和D2激动剂联合处理并未增强D1激动剂的作用。单独的黑质纹状体DA通路6-OHDA损伤降低了纹状体和黑质中强啡肽的水平。然而，反复注射D1激动剂而非D2激动剂不仅逆转了强啡肽水平的降低，还使其显著高于对照水平。在完整大鼠中，单独反复注射D1或D2拮抗剂未能改变强啡肽水平，但D1拮抗剂而非D2拮抗剂减弱了阿扑吗啡诱导的纹状体强啡肽增加。（摘要截于250字）
