Watanabe S, Aono Y, Fusa K, Takada K, Saigusa T, Koshikawa N, Cools A R
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Neuroscience. 2005;136(1):251-7. doi: 10.1016/j.neuroscience.2005.07.041. Epub 2005 Sep 21.
Systemic administration of high doses of dexamphetamine induces a dopamine efflux that has its intracellular origin in both the vesicular, reserpine-sensitive dopamine pool and the cytosolic, alpha-methyl-para-tyrosine-sensitive, newly synthesized dopamine pool. It remains unknown whether locally administered dexamphetamine produces similar effects. Using a brain microdialysis technique that is combined with a microinjection needle, the contribution of the vesicular and cytosolic pools to the dopamine efflux induced by striatal injection of dexamphetamine was analyzed in rats. The transient striatal dopamine efflux induced by intrastriatal injection of dexamphetamine (1.0 microg/0.5 microl) was significantly reduced by systemic administration of reserpine (5mg/kg i.p., given 24 h earlier) or alpha-methyl-para-tyrosine (250 mg/kg i.p., given 2 h earlier). The effects of dexamphetamine on the striatal dopamine were nearly nullified by combined treatment with reserpine and alpha-methyl-para-tyrosine. The sum of the amounts of extracellular dopamine that was sensitive to either reserpine or alpha-methyl-para-tyrosine, was far greater than 100%, namely 146.1% of the basal dopamine level and 144.0% of the dexamphetamine-induced dopamine level. The present study indicates that both the vesicular dopamine pool and the cytosolic dopamine pool contribute to the transient increase of striatal dopamine efflux induced by intrastriatal injection of dexamphetamine. This study also suggests that striatally applied dexamphetamine can promote the redistribution of rat striatal dopamine from vesicles to the cytosol in vivo.
大剂量右旋苯丙胺的全身给药会诱导多巴胺外流，其细胞内来源包括囊泡中对利血平敏感的多巴胺池和胞质中对α-甲基-对酪氨酸敏感的新合成多巴胺池。局部给药的右旋苯丙胺是否产生类似效果尚不清楚。使用与微量注射针相结合的脑微透析技术，分析了大鼠纹状体内注射右旋苯丙胺诱导的多巴胺外流中囊泡池和胞质池的作用。纹状体内注射右旋苯丙胺（1.0微克/0.5微升）诱导的短暂纹状体多巴胺外流，在全身给予利血平（5毫克/千克腹腔注射，提前24小时给予）或α-甲基-对酪氨酸（250毫克/千克腹腔注射，提前2小时给予）后显著降低。利血平和α-甲基-对酪氨酸联合处理几乎消除了右旋苯丙胺对纹状体多巴胺的作用。对利血平或α-甲基-对酪氨酸敏感的细胞外多巴胺量之和远大于100%，即基础多巴胺水平的146.1%和右旋苯丙胺诱导的多巴胺水平的144.0%。本研究表明，囊泡多巴胺池和胞质多巴胺池都促成了纹状体内注射右旋苯丙胺诱导的纹状体多巴胺外流的短暂增加。该研究还表明，纹状体内应用的右旋苯丙胺可促进大鼠纹状体多巴胺在体内从囊泡向胞质的重新分布。
