Whitehead K J, Rose S, Jenner P
Neurodegenerative Diseases Research Centre, Hodgkin Building, Guy's King's and St. Thomas's School of Biomedical Sciences, King's College, Guy's Campus, London, United Kingdom.
Neurochem Res. 2004 Apr;29(4):835-42. doi: 10.1023/b:nere.0000018858.64265.e9.
Microdialysis of the striatum of halothane-anesthetized rats was used to study the participation of local cholinergic and GABAergic neurotransmission in NMDA receptor-modulated striatal dopamine release and metabolism. Reverse dialysis.of NMDA (1 mM) evoked a 10-fold increase in dopamine efflux and reduced DOPAC and HVA to > 20% of basal values. The effect of NMDA on dopamine efflux was abolished by atropine (10 microM) but unaffected by (+)-bicuculline (50 microM). NMDA-induced decrease in DOPAC (but not HVA) efflux was potentiated by atropine, whereas (+)-bicuculline attenuated the decrease in DOPAC and HVA. Compared to our previous studies in unanesthetised rats, our data suggest that halothane anesthesia alters the balance between NMDA-stimulated cholinergic and GABAergic influences on striatal dopamine release and metabolism. Differential sensitivity to halothane of NMDA receptors expressed by the neurones mediating these modulatory influences, or loss of specific NMDA receptor populations through voltage-dependent Mg2+ block under anesthesia, could underlie these observations.
采用对氟烷麻醉大鼠纹状体进行微透析的方法,研究局部胆碱能和γ-氨基丁酸能神经传递在N-甲基-D-天冬氨酸(NMDA)受体调节的纹状体多巴胺释放及代谢中的作用。反向透析NMDA(1 mM)可使多巴胺流出量增加10倍,并使3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)降至基础值的20%以上。阿托品(10 microM)可消除NMDA对多巴胺流出的作用,但(+)-荷包牡丹碱(50 microM)对其无影响。阿托品可增强NMDA诱导的DOPAC(而非HVA)流出量的减少,而(+)-荷包牡丹碱可减弱DOPAC和HVA的减少。与我们之前对未麻醉大鼠的研究相比,我们的数据表明,氟烷麻醉改变了NMDA刺激的胆碱能和γ-氨基丁酸能对纹状体多巴胺释放及代谢影响之间的平衡。介导这些调节作用的神经元所表达的NMDA受体对氟烷的敏感性不同,或在麻醉状态下通过电压依赖性Mg2+阻断导致特定NMDA受体群体丧失,可能是这些观察结果的基础。