Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, MI 48109-1043, USA.
Neurosci Lett. 2011 Oct 17;504(1):13-7. doi: 10.1016/j.neulet.2011.08.028. Epub 2011 Aug 24.
In addition to blocking dopamine (DA) uptake, cocaine also causes an unconditioned increase in DA release. In drug naive rats, this effect is most robust within the nucleus accumbens (NAc) shell. Recent studies have shown that, in rats trained to self-administer cocaine, cocaine may act in the periphery to enhance mesolimbic DA release. Further, these studies have suggested that peripheral cocaine action may also enhance unconditioned DA release. Here, we test if it is necessary for cocaine to enter the brain to evoke unconditioned increases in DA release within the NAc shell. Administration of a cocaine analogue that crosses the blood brain barrier (cocaine HCl) enhances electrically evoked DA release and the number of cocaine-evoked phasic DA release events (i.e., DA transients) within the NAc shell. However, administration of a cocaine analogue that does not cross the blood brain barrier (cocaine MI) does not alter either measure. We therefore conclude that cocaine must act within the central nervous system to evoke unconditioned DA release within the NAc shell.
除了阻断多巴胺（DA）摄取外，可卡因还会引起未条件反射的 DA 释放增加。在未接受药物处理的大鼠中，这种作用在伏隔核（NAc）壳内最为明显。最近的研究表明，在接受可卡因自我给药训练的大鼠中，可卡因可能在外周发挥作用，增强中脑边缘 DA 释放。此外，这些研究还表明，外周可卡因作用也可能增强未条件反射的 DA 释放。在这里，我们测试可卡因是否必须进入大脑才能在 NAc 壳内引起未条件反射的 DA 释放增加。给予可穿过血脑屏障的可卡因类似物（盐酸可卡因）可增强电刺激诱发的 DA 释放，以及 NAc 壳内可卡因诱发的相位性 DA 释放事件（即 DA 瞬变）的数量。然而，给予不可穿过血脑屏障的可卡因类似物（可卡因 MI）则不会改变这两种测量值。因此，我们得出结论，可卡因必须在中枢神经系统内发挥作用，才能在 NAc 壳内引起未条件反射的 DA 释放。
