佐替平对家兔齿状回兴奋性突触反应和长时程增强的影响

目的 观察佐替平对家兔齿状回神经元兴奋性突触反应和长时程增强(LTP)的影响作用.方法 20只成年雄性家兔(体质量2.5～3.5 kg),按随机数字表法分为对照组和佐替平1.0组、佐替平2.0组、佐替平5.0组,每组各5只.每只家兔在120分钟里,共有60次记录结果.以群峰电位(PS)幅度和兴奋性突触后电位(EPSP)斜率作为齿状回神经元突触反应的观察指标.各组开始时记录基础反应,30min时分别腹腔注射二甲基亚砜0.5ml和佐替平-二甲基亚砜溶液0.5ml(佐替平的剂量依次为1.0mg/kg、2.0mg/kg、5.0mg/kg),90min时给予强直刺激,并记录相应的反应.结果 4组在单刺激前后的PS幅度和EPSP斜率均无显著性改变;对照组的PS幅度和EPSP斜率在强直刺激后[分别为(0.678±0.052)mV和(0.633±0.024)mV/ms]与注射前[分别为(0.266±0.008)mV和(0.246±0.010)mV/ms]相比有显著性差异(P＜0.05,P＜0.01),产生LTP;强直刺激后,佐替平1.0组、2.0组、5.0组均不产生LTP;佐替平5.0组强直刺激后的PS幅度和EPSP斜率[分别为(0.277±0.008)mV和(0.296±0.007)mV/ms]与对照组的同阶段结果相比有显著性差异(P＜0.05).结论 佐替平对单刺激家兔海马穿通纤维引起的兴奋性突触反应强度无影响作用,却能抑制家兔海马穿通纤维齿状回通路LTP的产生.

The impact of zotepine on the excitatory synaptic response and long-term potentiation in the hippocampus of rabbits

Objective To observe the impact of zotepine on the excitatory synaptic response and long term potentiation (LTP) of dentate gyrus neurons.Methods Male rabbits ( n = 20) weighting about 2.5 ～ 3.5 kg were divided into four groups randomly ( n = 5 ): control, zotepine 1.0, zotepine 2.0 and zotepine 5.0.To each rabbit,there were 60 results during 120 min.Population spike(PS) amplitude and excitory postsynaptic potential (EPSP) slope were used to be the indexes of the excitatory synaptic response of dentate gyrus neurons.The sequence was base response ( at the beginning), intraperitoneal injection of 0.5ml dimethylsulfoxide or 0.5ml zotepine-dimethylsulfoxide solution ( 1.0,2.0,5.0 mg/kg of zotepine dosage) ( after 30 min) and titanic stimulation (after 90 min).Results To 4 groups,the PS amplitude and EPSP slope after single stimuli were not significantly different from those before single stimuli.In control group, the PS amplitude and EPSP slope after titanic stimulation[(0.68 ± 0.052)mV and(0.633 ± 0.024 )mV/ms] were significantly different from those before injection[(0.266 ±0.008) mV and(0.246 ±0.010) mV/ms] (P＜0.05 ～0.01 ) ,and LTP were induced.LTP were not induced after titanic stimulation in group zotepine 1.0,2.0 and 5.0.After titanic stimulation, the PS amplitude and EPSP slope in group zotepine 5.0[(0.277 ±0.008)mV and(0.296 ±0.007) mV/ms] were significantly different from those in group control(P＜ 0.05).Conclusion Zotepine had little effect on the excitatory synaptic response of dentate gyrus neurons after single stimuli in perforant path, while it blocked the induction of LTP in perforant path-dentate gyrus pathway.