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作者机构:Univ Colorado Hlth Sci Ctr Dept Psychiat Denver CO 80262 USA Univ Colorado Hlth Sci Ctr Dept Pharmacol Denver CO 80262 USA Univ Colorado Hlth Sci Ctr Neurosci Training Program Denver CO 80262 USA Univ Colorado Hlth Sci Ctr Rocky Mt Ctr Sensor Technol Denver CO 80262 USA
出 版 物:《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)
年 卷 期:1999年第288卷第3期
页 面:1334-1339页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金:NIA NIH HHS [AG06434] Funding Source: Medline NIDA NIH HHS [DA04216] Funding Source: Medline NINDS NIH HHS [NS09199] Funding Source: Medline
主 题:年龄因素 放射自显影术 结合 竞争性 脑/代谢 载体蛋白质类/代谢 可卡因/类似物和衍生物 可卡因/代谢 多巴胺质膜转运蛋白质类 多巴胺摄取抑制剂/代谢 膜糖蛋白类 膜转运蛋白质类 神经组织蛋白质类 诺米芬辛/代谢 伏核/代谢 大鼠 近交F344 黑质/代谢 氚 腹侧被盖区/代谢 动物 男(雄)性 大鼠
摘 要:In the present study, we used the potent cocaine analog [H-3]WIN 35,428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [H-3]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%. However, significant age-related decreases in the overall density (B-max) of [H-3]WIN 35,428-binding sites were observed in the striatum, nucleus accumbens, substantia nigra, and ventral tegmental area. The B-max within all brain regions declined by more than 15% every 6 months, with the B-max in the aged (24-month-old) group being approximately halt that measured in the young adult (6-month-old) group. Competition experiments indicated that nomifensine also exhibited two-site binding to the DAT in Fischer 344 rats. No consistent age-related differences in binding affinities were noted with either [H-3]WIN 35,428 or nomifensine. Taken together, these results support the hypothesis that functional DATs within the nigrostriatal and mesolimbic systems are down-regulated with age, without changing their affinity for ligands.