Hondo H, Nakahara T, Nakamura K, Hirano M, Uchimura H, Tashiro N
Laboratory of Neurochemistry, Hizen National Mental Hospital, Kanzaki Saga, Japan.
Brain Res. 1995 Feb 6;671(1):54-62. doi: 10.1016/0006-8993(94)01319-d.
The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic (GABAergic) transmission in the striatum of freely-moving rats was investigated using an in vivo microdialysis. The high potassium (100 mM) increased the extracellular GABA level to 4000% of the basal level. Although the basal GABA level in the striatal dialysate did not show either calcium dependency or tetrodotoxin (TTX) sensitivity, the high potassium evoked GABA level was reduced by 82% under calcium-free conditions (with 12.5 mM magnesium) and by 54% in the presence of 10 microM TTX. The systemic administration of PCP (7.5 mg/kg) or the local perfusion of PCP (100 microM and 1 mM) significantly inhibited the high potassium evoked GABA release in the rat striatum. The local perfusion of MK-801 (10 microM and 100 microM), a more potent and selective N-methyl-D-aspartate (NMDA) receptor antagonist, also inhibited the high potassium evoked striatal GABA release. These drugs did not show any significant effect on the basal extracellular GABA level. NMDA (1 mM) either partly or completely blocked the effect of PCP (1 mM) or MK-801 (100 microM) on the high potassium evoked striatal GABA release. On the other hand, nomifensine (100 microM), a dopamine uptake blocker, did not show any effect on the high potassium evoked GABA release. These results suggest that PCP inhibited the striatal GABAergic neuronal transmission through its antagonism of the NMDA receptor.
使用体内微透析技术研究了苯环己哌啶（PCP）对自由活动大鼠纹状体中γ-氨基丁酸能（GABAergic）传递的影响。高钾（100 mM）使细胞外GABA水平增加至基础水平的4000%。尽管纹状体透析液中的基础GABA水平既不显示钙依赖性也不显示河豚毒素（TTX）敏感性，但在无钙条件下（含12.5 mM镁），高钾诱发的GABA水平降低了82%，在存在10 μM TTX的情况下降低了54%。全身给予PCP（7.5 mg/kg）或局部灌注PCP（100 μM和1 mM）显著抑制了大鼠纹状体中高钾诱发的GABA释放。局部灌注MK-801（10 μM和100 μM），一种更有效且选择性更高的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，也抑制了高钾诱发的纹状体GABA释放。这些药物对基础细胞外GABA水平没有任何显著影响。NMDA（1 mM）部分或完全阻断了PCP（1 mM）或MK-801（100 μM）对高钾诱发的纹状体GABA释放的作用。另一方面，多巴胺摄取阻滞剂诺米芬辛（100 μM）对高钾诱发的GABA释放没有任何影响。这些结果表明，PCP通过拮抗NMDA受体抑制了纹状体GABA能神经元传递。
