Wang Zhixia, Ordway Gregory A, Woolverton William
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Neurosci Lett. 2007 Feb 21;413(3):191-5. doi: 10.1016/j.neulet.2006.11.041. Epub 2006 Dec 13.
The increase in extracellular dopamine (DA) following cocaine administration plays a major role in cocaine abuse. In vitro, cocaine binds to DA transporters (DAT) and blocks DA uptake. Moreover, cocaine can increase extracellular DA concentration as measured by in vivo neurochemical methods. The present study examined the effects of cocaine and other drugs on DA, NE and 5-HT uptake using an ex vivo assay. Rats were injected i.v. with saline or drug and sacrificed at various time points after injections. Brains were dissected for regional monoamine uptake studies ex vivo. In most brain regions, cocaine given in vivo blocked monoamine uptake as expected. [3H]DA uptake in nucleus accumbens was inhibited with an ED50=22.3 micromol/kg. Cocaine fully inhibited [3H]NE uptake (ED50=4.58 micromol/kg) in the occipital cortex and partially inhibited [3H]5-HT uptake (33% at 30 micromol/kg) in the midbrain. However, under the same conditions [3H]DA uptake in the striatum was not inhibited after injections of cocaine up to 56 micromol/kg. Although the mechanism for this discrepancy is unclear, DA binding and uptake sites may be distinct and/or there may be regional differences in DA transporters.
可卡因给药后细胞外多巴胺（DA）的增加在可卡因滥用中起主要作用。在体外，可卡因与DA转运体（DAT）结合并阻断DA摄取。此外，可卡因可通过体内神经化学方法测量增加细胞外DA浓度。本研究使用离体试验研究了可卡因和其他药物对DA、去甲肾上腺素（NE）和5-羟色胺（5-HT）摄取的影响。大鼠静脉注射生理盐水或药物，并在注射后的不同时间点处死。解剖大脑用于离体区域单胺摄取研究。在大多数脑区，体内给予可卡因如预期那样阻断了单胺摄取。伏隔核中[3H]DA摄取受到抑制，半数有效剂量（ED50）=22.3微摩尔/千克。可卡因完全抑制枕叶皮质中[3H]NE摄取（ED50=4.58微摩尔/千克），并部分抑制中脑[3H]5-HT摄取（30微摩尔/千克时为33%）。然而，在相同条件下，注射高达56微摩尔/千克可卡因后，纹状体中[3H]DA摄取未受到抑制。尽管这种差异的机制尚不清楚，但DA结合和摄取位点可能不同，和/或DA转运体可能存在区域差异。
