Yonezawa Y, Kuroki T, Kawahara T, Tashiro N, Uchimura H
Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1998 Jan 2;341(1):45-56. doi: 10.1016/s0014-2999(97)01435-0.
The present study was designed to examine the possible involvement of gamma-aminobutyric acid (GABA) neurotransmission in the mechanism of phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced dopamine release in the medial prefrontal cortex, using in vivo microdialysis in awake, freely moving rats. Local perfusion via the dialysis probe into the medial prefrontal cortex with PCP (100 and 500 microM) and dizocilpine ((+)-5-methyl-10,11-dihydroxy-5-H-dibenzo(a,d)cyclo-heptan-5,10-im ine; MK-801, 10 and 50 microM), a selective non-competitive NMDA receptor antagonist, was found to increase extracellular dopamine levels. Co-perfusion with NMDA (1 mM) or the GABAA receptor agonist muscimol (50 microM) attenuated the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular dopamine levels. The dopamine reuptake inhibitor nomifensine (50 microM) also produced an increase in extracellular dopamine levels in the medial prefrontal cortex, but this effect was not affected by co-perfusion with muscimol (50 microM). On the other hand, local perfusion with PCP (100 and 500 microM) and MK-801 (10 and 50 microM), but not nomifensine (50 microM), reduced extracellular GABA levels in the medial prefrontal cortex. Co-perfusion with NMDA (1 mM) reduced the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular GABA levels. These results suggest that PCP may facilitate dopamine release in the medial prefrontal cortex, at least in part, by the inhibition of GABA release via the antagonism of NMDA receptors.
本研究旨在通过对清醒、自由活动的大鼠进行体内微透析，研究γ-氨基丁酸（GABA）神经传递是否参与苯环己哌啶（1-（1-苯基环己基）哌啶；PCP）诱导的内侧前额叶皮质多巴胺释放机制。通过透析探针向内侧前额叶皮质局部灌注PCP（100和500微摩尔）和地佐环平（（+）-5-甲基-10,11-二羟基-5-H-二苯并（a,d）环庚烷-5,10-亚胺；MK-801，10和50微摩尔），一种选择性非竞争性NMDA受体拮抗剂，发现可增加细胞外多巴胺水平。与NMDA（1毫摩尔）或GABAA受体激动剂蝇蕈醇（50微摩尔）共同灌注可减弱PCP（500微摩尔）和MK-801（50微摩尔）对细胞外多巴胺水平的影响。多巴胺再摄取抑制剂诺米芬辛（50微摩尔）也可使内侧前额叶皮质细胞外多巴胺水平升高，但这种作用不受与蝇蕈醇（50微摩尔）共同灌注的影响。另一方面，向内侧前额叶皮质局部灌注PCP（100和500微摩尔）和MK-801（10和50微摩尔），但不包括诺米芬辛（50微摩尔），可降低细胞外GABA水平。与NMDA（1毫摩尔）共同灌注可减弱PCP（500微摩尔）和MK-801（50微摩尔）对细胞外GABA水平的影响。这些结果表明，PCP可能至少部分通过拮抗NMDA受体抑制GABA释放，从而促进内侧前额叶皮质多巴胺释放。
