Acworth I N, During M J, Wurtman R J
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Brain Res Bull. 1988 Sep;21(3):473-7. doi: 10.1016/0361-9230(88)90161-x.
Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.
给予加速黑质纹状体放电的治疗的动物,酪氨酸给药可提高纹状体中多巴胺代谢物的水平,但未治疗的大鼠则不然。我们研究了这种氨基酸实际上可能增强未治疗动物体内多巴胺释放的可能性,但测量纹状体多巴胺代谢的技术过于不敏感,无法证明这种效应。使用纹状体细胞外液的脑微透析直接评估多巴胺释放。酪氨酸给药(50-200mg/kg腹腔注射)确实导致细胞外液多巴胺水平呈剂量相关增加,其主要代谢物DOPAC和HVA水平略有升高,但与剂量无关。多巴胺的升高是短暂的,这表明受体介导的反馈机制通过减少神经元放电或对酪氨酸的敏感性来应对多巴胺释放的增加。这些观察结果表明,如果纹状体DOPAC和HVA的变化测量结果为阴性,并不一定排除黑质纹状体多巴胺释放增加的可能性。