Elsworth J D, Taylor J R, Berger P, Roth R H
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Neurochem Int. 1993 Jul;23(1):61-9. doi: 10.1016/0197-0186(93)90144-t.
Behavioral studies have indicated that the reinforcing effects of cocaine are dependent on inhibition of dopamine uptake in nucleus accumbens and prefrontal cortex. As it has been suggested that dopamine uptake and cocaine-inhibition of dopamine uptake may differ in nucleus accumbens, prefrontal cortex and striatum, we have further characterized dopamine uptake and its susceptibility to inhibition in these three regions. Dopamine uptake was resolved into two processes, which accounts for some of the apparent reported regional differences in sensitivity of dopamine to inhibition by cocaine. One, which is probably associated with uptake into dopaminergic terminals, was sensitive to 6-hydroxydopamine lesions, cocaine, GBR 12909 or ouabain and was dependent on temperature and sodium ion concentration; this was responsible for most of the observed uptake in tissue from striatum and nucleus accumbens, but not from prefrontal cortex. There appeared to be no regional difference in susceptibility of this mode of dopamine uptake to either cocaine or GBR 12909. The other type of dopamine uptake, which represented a significant proportion of the total in prefrontal cortex, but not in striatum or nucleus accumbens, was relatively insensitive to cocaine, GBR 12909 and ouabain and was dependent on temperature, but not sodium ion concentration. In addition, the cocaine-insensitive dopamine uptake was more sensitive to inhibition by dopamine than serotonin, but did not distinguish between dopamine and norepinephrine. The occurrence of cocaine-sensitive dopamine uptake in all examined regions and its equal sensitivity to cocaine and GBR 12909 is consistent with the involvement of nucleus accumbens and/or prefrontal cortex in the reinforcing effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
行为学研究表明，可卡因的强化作用取决于对伏隔核和前额叶皮质中多巴胺摄取的抑制。由于有人提出多巴胺摄取及可卡因对多巴胺摄取的抑制在伏隔核、前额叶皮质和纹状体中可能存在差异，我们进一步对这三个区域的多巴胺摄取及其对抑制的敏感性进行了表征。多巴胺摄取可分为两个过程，这解释了一些关于多巴胺对可卡因抑制敏感性的明显区域差异报道。一个过程可能与多巴胺能终末的摄取相关，对6 - 羟基多巴胺损伤、可卡因、GBR 12909或哇巴因敏感，且依赖于温度和钠离子浓度；这是纹状体和伏隔核组织中大部分观察到的摄取的原因，但在前额叶皮质中并非如此。这种多巴胺摄取模式对可卡因或GBR 12909的敏感性似乎不存在区域差异。另一种多巴胺摄取类型，在前额叶皮质中占总量的很大比例，但在纹状体或伏隔核中并非如此，对可卡因、GBR 12909和哇巴因相对不敏感，依赖于温度，但不依赖于钠离子浓度。此外，对可卡因不敏感的多巴胺摄取对多巴胺抑制的敏感性高于血清素，但无法区分多巴胺和去甲肾上腺素。在所有检测区域中均存在对可卡因敏感的多巴胺摄取，且其对可卡因和GBR 12909的敏感性相同，这与伏隔核和/或前额叶皮质参与可卡因的强化作用一致。（摘要截断于250字）
