Akiyama Y, Ito A, Koshimura K, Ohue T, Yamagata S, Miwa S, Kikuchi H
Department of Neurosurgery, Kyoto University Faculty of Medicine, Japan.
Brain Res. 1991 Oct 4;561(1):120-7. doi: 10.1016/0006-8993(91)90756-l.
To clarify functional changes of dopaminergic neurons and dopamine (DA) reuptake during and after ischemia, extracellular DA levels in striatum were determined using in vivo brain microdialysis in a 4-vessel occlusion model of male Wistar rats with and without pharmacological interventions. Without interventions, the extracellular DA levels markedly increased during ischemia, but upon reperfusion, rapidly returned to control level. Infusion of tetrodotoxin, a blocker of voltage-dependent Na+ channels, was without effect on the DA surge during ischemia, but decreased the DA levels after reperfusion to the same extent as in control rats. Pretreatment with nomifensine, an inhibitor of DA reuptake, was also without effect on the surge, but reduced the rate of DA decline after reperfusion to one-fifth of the rate without the pretreatment. When nomifensine was administered 40 min after reperfusion, extracellular DA levels increased to the same extent as in control rats. Infusion of high K+ 1 h after reperfusion induced a smaller increase in extracellular DA levels than that in control rats. It took 96 h for this reduced response to high K+ stimulation to recover after reperfusion. These results suggest that the DA surge during ischemia is mainly derived from action potential-independent DA release (means dysfunction of dopaminergic neurons), although activity of DA reuptake is completely inhibited. After reperfusion, the basal function of dopaminergic neurons and activity of DA reuptake rapidly recover, but the neurons are functionally disturbed to release less DA in response to a given stimulus for several days.
为阐明缺血期间及之后多巴胺能神经元的功能变化以及多巴胺（DA）再摄取情况，我们在雄性Wistar大鼠的四动脉闭塞模型中，采用活体脑微透析技术，在有或没有药物干预的情况下，测定纹状体细胞外DA水平。在没有干预的情况下，缺血期间细胞外DA水平显著升高，但再灌注时，迅速恢复到对照水平。注入电压依赖性Na⁺通道阻滞剂河豚毒素，对缺血期间的DA激增没有影响，但使再灌注后的DA水平下降程度与对照大鼠相同。用DA再摄取抑制剂诺米芬辛预处理，对激增也没有影响，但使再灌注后DA下降速率降至未预处理时的五分之一。在再灌注40分钟后给予诺米芬辛，细胞外DA水平升高至与对照大鼠相同的程度。再灌注1小时后注入高钾，诱导的细胞外DA水平升高幅度小于对照大鼠。再灌注后，这种对高钾刺激反应降低的情况需要96小时才能恢复。这些结果表明，缺血期间的DA激增主要源于与动作电位无关的DA释放（意味着多巴胺能神经元功能障碍），尽管DA再摄取活性被完全抑制。再灌注后，多巴胺能神经元的基础功能和DA再摄取活性迅速恢复，但在数天内，神经元在功能上受到干扰，对给定刺激释放的DA减少。
