Shah N S, Shah A B
Dev Pharmacol Ther. 1984;7(2):109-20.
Albino Sprague-Dawley rats (1, 8, 12 and 20 days old) were injected intraperitoneally with l-[3H-1]-methadone (5 mg/kg containing 50 muCi/kg), and sacrificed at 15 min, 1 h and 3 h. Whole brain was homogenized in 0.32 M sucrose-Tris buffer and the homogenates were subjected to differential centrifugation to separate nuclei, mitochondria, microsomes, soluble cytosol, myelin, membrane and synaptosomes. Methadone levels in each fraction were examined. The methadone contents in the whole brain (sum of all fractions) of 1- and 8-day-old rats were significantly higher relative to those of 12- and 20-day-old rats at all time intervals. The most striking finding in this study was that during development, the percentage of methadone content in the synaptosomal fraction progressively increased relative to other subcellular fractions; interestingly, there was an associated decrease in the percent levels in the soluble cytosol suggesting a shift of methadone from cytosol to synaptosomes. These alterations in brain synaptosomal accumulation of methadone could result from the progressive increase in the affinity of methadone for synaptosomes as these particles become enriched in the protein and lipid contents and possibly increase in opiate receptor density during the neuronal maturation and the synaptogenesis of the developing brain.
将白化斯普拉格-道利大鼠（1日龄、8日龄、12日龄和20日龄）腹腔注射l-[3H-1]-美沙酮（5毫克/千克，含50微居里/千克），并于15分钟、1小时和3小时后处死。将全脑在0.32M蔗糖- Tris缓冲液中匀浆，匀浆经差速离心以分离细胞核、线粒体、微粒体、可溶性胞质溶胶、髓磷脂、膜和突触体。检测各组分中美沙酮水平。在所有时间间隔，1日龄和8日龄大鼠全脑（所有组分总和）中的美沙酮含量相对于12日龄和20日龄大鼠显著更高。本研究中最显著的发现是，在发育过程中，相对于其他亚细胞组分，突触体组分中美沙酮含量的百分比逐渐增加；有趣的是，可溶性胞质溶胶中百分比水平相应降低，表明美沙酮从胞质溶胶转移至突触体。随着发育中大脑神经元成熟和突触形成过程中这些颗粒的蛋白质和脂质含量增加以及阿片受体密度可能升高，美沙酮对突触体的亲和力逐渐增加，可能导致了大脑突触体中美沙酮积累的这些变化。
