Shiraishi M, Kamiyama Y, Hüttemeier P C, Benveniste H
Department of Anesthesiology, Juntendo University Urayasu Hospital, Tokyo, Japan.
Brain Res. 1997 Jun 13;759(2):221-7. doi: 10.1016/s0006-8993(97)00258-8.
We investigated the effect of high dose tetrodotoxin (TTX) on microdialysis measurements of extracellular striatal glutamate and dopamine in normal female rats. Both halothane-anesthetized rats with acutely implanted microdialysis probes and awake rats with microdialysis probes implanted for 24 h were tested. Glutamate levels in awake rats were 45% higher than those of anesthetized rats. Extracellular glutamate remained TTX-insensitive regardless of TTX concentration, anesthesia, or time lapsed after probe implantation. In contrast, TTX reduced dialysate dopamine in all TTX concentrations tested. We speculate that the lower glutamate levels in anesthetized rats reflect the effect of anesthesia. Because glutamate is involved, either as a reactant or a product in a variety of reactions critical to intermediary metabolism in the brain, basal dialysate glutamate levels might indirectly reflect brain metabolism. Further, we conclude that extracellular glutamate collected during non-stimulated conditions is TTX-insensitive. The fact that glutamate levels are TTX-independent does not rule out that glutamate is synaptic in origin but rather demonstrates that it is not nerve impulse-dependent. However, the brain interstitial glutamate pool accessible to the microdialysis probe during control conditions is most likely isolated from the synapse, and therefore does not impose a neurotoxic potential.
我们研究了高剂量河豚毒素（TTX）对正常雌性大鼠纹状体细胞外谷氨酸和多巴胺微透析测量的影响。对急性植入微透析探针的氟烷麻醉大鼠和植入微透析探针24小时的清醒大鼠均进行了测试。清醒大鼠的谷氨酸水平比麻醉大鼠高45%。无论TTX浓度、麻醉状态或探针植入后的时间间隔如何，细胞外谷氨酸对TTX均不敏感。相比之下，在所测试的所有TTX浓度下，TTX均降低了透析液中的多巴胺水平。我们推测麻醉大鼠中较低的谷氨酸水平反映了麻醉的作用。由于谷氨酸作为反应物或产物参与了大脑中间代谢中各种关键反应，基础透析液谷氨酸水平可能间接反映大脑代谢。此外，我们得出结论，在非刺激条件下收集的细胞外谷氨酸对TTX不敏感。谷氨酸水平与TTX无关这一事实并不排除谷氨酸起源于突触，而是表明它不依赖于神经冲动。然而，在对照条件下微透析探针可接触到的脑间质谷氨酸池很可能与突触隔离，因此不具有神经毒性潜力。
