纳洛酮对大鼠额叶皮质神经元兴奋性的影响(英文)

Effect of naloxone on neuronal excitability in rat frontal lobe cortex

背景:纳洛酮的促醒机制不可能完全是因为抑制内源性阿片肽所致,所以进一步探讨纳洛酮逆转昏迷作用的神经药理机制,具有重要意义。目的:观察促醒剂纳洛酮对大鼠额叶皮质神经元兴奋性的影响,以了解纳洛酮是否通过非阿片受体抑制机制发挥促醒作用。设计:两因素析因设计。单位:解放军第一六一中心医院神经内科;华中科技大学同济医学院同济医院神经内科。材料:实验于2003-12/2004-04在华中科技大学同济医学院实验中心完成。选取出生8～12d健康Wistar大鼠30只,体质量150～250g,雌雄不限。方法:实验在20～24℃的室温下进行。选择表面光洁,胞体呈三角形或锥形且折光性强,有一个以上突起的神经元进行膜片钳实验。实验给药方法包括灌流给药(γ氨基丁酸)和压力喷射给药(谷氨酸和纳洛酮等)。主要观察指标:谷氨酸和γ氨基丁酸及纳洛酮对急性分离的FCX锥体细胞兴奋性的影响。结果:急性分离的皮质神经元能对兴奋性性神经递质谷氨酸和抑制性神经递质γ氨基丁酸产生正常反应。电流钳记录模式下,纳洛酮(0.1mmol/L)使额叶皮质神经元去极化伴动作电位发放频率增加,电压钳记录模式下,纳洛酮(0.1mmol/L)使神经元产生内向电流(13/14)。结论:纳洛酮对皮质神经元具有直接兴奋作用,提示其可通过直接兴奋皮质,发挥逆转昏迷。

BACKGROUND:The mechanism of naloxone is still unclear due to the inhibition of endogenous opioids. It is important to further study its pharmacologic mechanis m that reverses coma. OBJECTIVE:To investigate the effect of naloxone on neuronal excitability in ra t frontal lobe cortex so as to explore whether the awakening effect of naloxone is mediated by non opioid receptor. DESIGN:Two factor factorial design. SETTING:The Neurological Department of the 161 Military Center Hospital and th e Neurological Department of Tongji Hospital,Tongji Medical College. MATERIALS:This study was completed at the Experimental Center of Tongji Medica l College from December 2003 to April 2004.Thirty healthy Wistar rats,without se x limitation,aged 8-12 days and weighted 150-250 g,were used. METHODS:This experiment was performed at room temperature of 20-24 ℃.Neuron of triangle or pyramid shape and with strong refractivity,clear surface,and more than one prominence was adopted for observation.Medicine was administered by in fusion(γ amido butyric acid) or alternatively press spray(glutamine and nalox one). MAIN OUTCOME MEASURES:Effect of glutamine,γ amido butyric acid(GABA),and nal oxone on the excitability of acutely isolated frontal cortex(FCX) pyramidal neur ons. RESULTS:Acutely isolated cortical neurons responsed normally to excitatory tra nsmitter glutamine and inhibitory transmitter GABA.In current clamp recording st ate,it was found that depolarization of frontal lobe neurons could be induced by 0.1 mmol/L naloxone,accompanied by increased delivery frequency of action poten tial(AP);in addition,inwards current was also observed in voltage clamp recordi ng state(13/14). CONCLUSION:Naloxone can directly excite cortical neurons, suggesting that nalo xone can directly excite cortex and play a role of reversing coma and awakening.