氯氮平对家兔海马齿状回突触传递及神经递质释放的影响

目的：观察给予氯氮平前后齿状回反应及细胞外多巴胺（DA）和5-羟色胺（5-HT）水平的变化规律。方法：15只成年家兔,将刺激用微电极置于海马穿通纤维处,记录用微电极和收集神经递质的引导插管置于同侧齿状回处,经10d康复后随机分为对照组（C组）、强直刺激组（T组）和无强直刺激组（N组）,每组各5只。整个实验180min,分3阶段（60min/阶段）。全程给予齿状回单极方脉冲电刺激,60min时分别腹腔注射20mg/kg氯氮平溶液（T组和N组）或空白溶剂（C组）,120min时给予强直刺激（C组和T组）。实验中,每隔2min记录一次齿状回反应,每隔5min检测一次齿状回细胞外DA和5-HT的水平。结果：齿状回反应：C组1、2阶段无改变（P〉0.05）,3阶段较1、2阶段增强（P=0.02）,产生长时程增强（LTP）;T组2阶段较1阶段增强（氯氮平增强）（P=0.004）,3阶段较2阶段进一步增强（P=0.02）,产生LTP;N组2阶段较1阶段增强（氯氮平增强）（P=0.004）,3阶段同2阶段（P〉0.05）。细胞外DA和5-HT的水平：C组的DA水平在3个阶段均无改变（P〉0.05）;T组2、3阶段DA水平较1阶段明显升高（P〈0.01）,但3阶段的DA水平却没有因LTP的产生而出现相应的改变;N组2、3阶段DA水平较1阶段明显升高（P〈0.01）;3组在全部实验中的5-HT水平均无改变（P〉0.05）。结论：氯氮平可在齿状回同步产生氯氮平增强和细胞外DA水平的增加。     

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

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.     

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.     

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

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.