2,5-二甲氧基-4-碘苯丙胺对卡巴胆碱诱导的小鼠离体海马CA3区γ振荡的作用

Effect of 2,5-dimethoxy-4-iodoamphetamine on carbachol-induced γ oscillations of hippocampal area CA3 in mice in vitro

目的探究5-羟色胺2A受体(5-HT_(2A)R)激动剂2,5-二甲氧基-4-碘苯丙胺(DOI)对卡巴胆碱(CCh)诱发的小鼠离体海马CA3区γ振荡的作用。方法制备C57BL/6J小鼠离体海马脑片,用人工脑脊液(ACSF)灌流,用离体脑片电生理法记录海马CA3区局部场电位(LFP),用NeuroExplorer软件分析LFP功率,用Matlab软件分析θ振荡和γ振荡的相位振幅耦合。离体海马脑片给予CCh 5μmol·L^(-1),记录给药前后海马CA3区LFP的变化,并给予荷包牡丹碱(Bic)5μmol·L^(-1)验证γ振荡的诱发。在CCh诱导产生γ振荡后给予DOI 10μmol·L^(-1),分析DOI对γ振荡功率的影响,计算θ振荡和γ振荡的相位振幅耦合调制指数(MI)。结果离体海马脑片给予CCh 5μmol·L^(-1)后,海马CA3区LFP功率较给药前显著升高(P<0.01);在此基础上给予Bic 5μmol·L^(-1)后,LFP功率较给Bic前显著降低(P<0.01),表明γ振荡诱发成功。给予DOI 10μmol·L^(-1)后,CCh诱发的γ振荡功率较给DOI前显著增加(P<0.05),θ振荡功率及θ振荡与γ振荡相位振幅耦合MI较给DOI前无显著差异。结论DOI可能是通过增加海马CA3区γ振荡功率,而非通过影响θ振荡或θ振荡与γ振荡相位振幅耦合发挥影响认知的药理学作用。

OBJECTIVE To study the effect of 5-hydroxytryptamine 2A(5-HT_(2A))receptor agonist 2,5-dimethoxy-4-iodoamphetamine(DOI)on carbachol(CCh)-inducedγoscillations of hippocampal area CA3 in vitro.METHODS C57BL/6J mice were chosen to prepare hippocampal brain slices and perfused by artificial cerebrospinal fluid(ACSF).The local field potential(LFP)was recorded using the brain slice electrophysiological method.LFP was analyzed by Neuro Explorer software,andθ-γcross-frequency phase-amplitude(CFPA)coupling was analyzed by Matlab.CCh 5μmol·L^(-1)was administered to record the changes of LFP in hippocampal area CA3 before and after administration,and bicuculline(Bic)5μmol·L^(-1)was given to verify the induction ofγoscillations.DOI 10μmol·L^(-1)was administered after CCh induced the generation ofγoscillations.The effect of DOI on the power ofγoscillations and the modulation index(MI)ofθ-γCFPA coupling were analyzed.RESULTS After administration of CCh 5μmol·L^(-1),the LFP power in hippocampal area CA3 increased significantly(P<0.01).When Bic 5μmol·L^(-1)was administered later,the LFP power decreased significantly(P<0.01),indicating thatγoscillations were successfully induced.After the administration of DOI 10μmol·L^(-1),the power of CCh inducedγoscillations increased significantly(P<0.05),while the power ofθoscillations and MI ofθ-γCFPA coupling did not change significantly.CONCLUSION DOI may exert pharmacological effect on cognition by increasing the power ofγoscillations in hippocampal area CA3 rather than by affectingθoscillations orθ-γCFPA coupling.