咪达唑仑对大鼠海马CA1区突触传递的影响

Effect of midazolam on synaptic transmission in rat hippocampal CA1 area

目的探讨咪达唑仑对大鼠海马CA1区突触传递的影响。方法成年雄性Wistar大鼠35只，体重190～220g，随机分为7组（n=5），单刺激下4组：对照组（C1组）、荷包牡丹碱组（B1组）、咪达唑仑组（M1组）和荷包牡丹碱＋咪达唑仑组（BM组）；配对刺激下3组：对照组（C2组）、荷包牡丹碱组（B2组）和咪达唑仑组（M2组）。单刺激条件：刺激方波波宽0．1ms、频率0．033Hz，配对刺激条件：刺激方波波宽0．1ms、频率0．033Hz，两个配对刺激间隔30ms，刺激强度为诱发兴奋性突触后电位（EPSP）峰值刺激强度的50％。C1,2组和M1,2组记录EPSP幅值的基础值，随后分别腹腔注射生理盐水3ml／kg和咪达唑仑3mg／kg；B1,2组和BM组记录EPSP幅值的基础值，随后腹腔注射荷包牡丹碱2mg／kg，20min后BM组腹腔注射咪达唑仑3mg／kg。各组给药结束后再记录60min，每10min为一时段。单刺激下计算各时间段EPSP幅值与基础值的比值即相对幅值，配对刺激下记录两个配对刺激下的EPSP幅值（分别为E1和E2），计算E2／E1。结果与C1组比较，M1组EPSP相对幅值降低（P〈0．05或0．01），B1组和BM组差异无统计学意义（P〉0．05）；与C2组比较，B2组E2及e2／E1升高（P〈0．05），E1差异无统计学意义（P〉0．05），M2组E1、E2及E2／E1均降低（P〈0．05）；与B2组比较，M2组E1、E2及E2／E1均降低（P〈0．05）。结论眯达唑仑可抑制大鼠海马CA1区兴奋性突触传递，呈可逆性，其机制可能与增强γ-氨基丁酸（GABA）能性突触前抑制性回路的兴奋性有关，而非直接影响GABA∧受体功能状态。

Objective To investigate the effect of midazolam on synaptic transmission in stratum radiatum of CA1 area of rat hippocampus and the underlying mechanism. Methods Thirty-five adult male Wistar rats weighing 190-220 g were randomly divided into 7 groups （ n = 5 each）. Two types of stimulation were used： single stimulation and paired pulse stimulation. Four groups under single stimulation： control group （group C1 ）, bieuculline group （group B1 ）, midazolam group （group M1 ） and bicueulline ＋ midazolam group （group BM）. Three groups under paired pulse stimulation： control group （group C2 ）, bieuculline group （group B2 ） and midazolam group （ group M2 ）. The animals were anesthetized with intraperitoneal （IP） pentobarbital 50 mg/kg. The stimulating and recording electrodes were inserted into the stratum radiatum of CA1 area of the hippocampus. The interval between the 2 pulse stimulation was 30 ms. Excitatory post-synaptic potential （EPSP） was elicited before （baseline） and after IP bicuculline （2 mg/kg） or/and midazolam （3 mg/kg） administration. The EPSP amplitude was recorded during single stimulation. EPSP2/EPSP1 （E2/E1） ratio was recorded during paired pulse stimulation. Results Compared with group C1 , the EPSP amplitude was significantly decreased in group M1 （ P 〈 0.05 or 0.01）, but no significant change was found in group Bt and BM （P 〉 0.05） . Compared with group C2 , E2 and E2/E1 ratio were significantly increased in group B2, while E2/E2 and E2/E1 ratio were significantly decreased in group M2 （P 〈 0.05）. E1/E2 and E2/E1 ratio were significantly lower in group M2 than in group B2 （P 〈 0.05）. Conclusion Midazolam can reversibly depress the excitatory synaptic transmission efficacy in the CA1 area of the rat hippocampus through presynaptic inhibitory circuit. CABA∧ receptor is not directly disturbed.