槟榔碱增强尼古丁在大鼠海马脑片CA1锥体细胞诱发PS2的作用

在大鼠离体海马脑片上，记录ＣＡ１锥体细胞外诱发群峰电位（ＰＳ），以灌流和局部微量注射两种给药途径，观察了槟榔碱（Ａｒｅ）与尼古丁（Ｎｉｃ）同时给药对ＰＳ的影响，研究胆碱能Ｍ和Ｎ受体之间的关系．结果表明，Ａｒｅ增强Ｎｉｃ诱发第二个群峰电位（ＰＳ２）的作用，这一作用不能被Ｍ受体拮抗剂阿托品（０．００１－０．１ｍｍｏｌ·Ｌ－１）或Ｎ受体拮抗剂美卡拉明（１．０ｍｍｏｌ·Ｌ－１）拮抗，兼具中枢胆碱Ｍ和Ｎ受体拮抗作用的贝那替秦（０．０１－０．１ｍｍｏｌ·Ｌ－１）能较好地预防这一作用，表明Ｍ和Ｎ受体之间存在有相互调节关系．     

石杉碱甲增强大鼠海马脑片CA1锥体神经元的兴奋性突触传递

目的:观察石杉碱甲(Hup-A)对海马CA1锥体神经元兴奋性突触传递的影响,以探讨其增强学习记忆功能的神经细胞电生理机制。方法:应用大鼠海马脑片CA1锥体神经元细胞内记录技术,观察Hup-A对大鼠海马CA1锥体神经元膜电性质和刺激Schaffer侧支诱发的兴奋性突触后电位(EPSP)的影响。结果:(1)Hup-A(1μmol/L)灌流15min对CA1锥体神经元的膜电性质没有显著性影响。(2)Hup-A(0.3～3.0μmol/L)浓度依赖性使EPSP幅度升高、时程延长、曲线下面积增大,该作用可被阿托品(10μmol/L)预处理取消。(3)Hup-A对外源性谷氨酸诱导的去极化反应无明显影响。结论:Hup-A可增强CA1锥体神经元的兴奋性突触传递,其增强突触传递作用与M型乙酰胆碱受体激动有关。     

石杉碱甲对大鼠海马脑片CA1神经元θ节律及长时程增强的影响

目的:研究石杉碱甲(HupA)对大鼠海马脑片CA1锥体神经元θ节律、长时程增强的影响,以分析其增强学习记忆功能的神经细胞电生理机制。方法:应用大鼠海马脑片神经元细胞内记录技术,观察石杉碱甲对大鼠海马脑片的CA1锥体神经元θ节律、长时程增强的影响。结果:(1)未用药组出现膜电位振荡前后4～10Hz(θ节律)功率分量之和无显著性差异,但在HupA(1μmol·L-1)灌流15min后出现膜电位振荡,与用药前没有膜电位振荡的4～10Hz功率分量之和配对t检验比较有显著差异(n=3,P<0.005)。(2)在LTP期间,对照组EPSP幅度在强直刺激后30min显著性的升高(P<0.05),而HupA组在强直刺激后15min即出现显著性升高(P<0.01)。结论:HupA可增加大海马锥体神经元在θ频率范围内的功率分量,并易化LTP的诱发,这可能是其增强学习记忆功能的细胞电生理机制之一。     

SC1001Na对马桑内酯点燃大鼠海马脑片CA1区锥体细胞群体锋电…

作者用离体海马脑片技术，从细胞水平观察及比较了ｓｃ１００１Ｎａ对马桑内酯点燃大鼠海马脑片ＣＡ１区群体锋电位（ＰＳ）的影响。结果表明：不同浓度的ｓｃ１００１Ｎａ和安定对ＰＳ均有抑制作用，其抑制作用在对照组两组比较有显著差异（Ｐ〈０．００１），而在点燃组无显著差异（Ｐ〉０．０５）。提示ｓｃ１００１Ｎａ具有较强的中枢抑制作用。但其作用机制可能与安定不同。     

加锡果宁抑制荷包牡丹碱在大鼠海马脑片CAl区诱发的痫样放电

在大鼠离体海马脑片标本表面灌流荷包牡丹碱(10μmol·L~(-1)),单脉冲电刺激Schaffer侧支,激活CAl区锥体细胞,给出痫样放电,作者在这种痫样放电模型上研究了加锡果宁对该痫样放电的影响,结果表明,微量推注不同浓度的加锡果宁到脑片CAl区表面,对荷包牡丹碱诱发的CAl区锥体细胞痫样放电呈剂量依赖性抑制,提示加锡果宁可对抗荷包牡丹碱的致痫作用,并讨论了可能机理。     

血管性痴呆小鼠海马CA1区锥体细胞形态结构及石杉碱甲对其影响

目的:观测血管性痴呆(VD)小鼠海马CA1区锥体细胞及石杉碱甲的治疗效果.方法:制作VD动物模型,并设立假手术组、石杉碱甲组;测试学习和记忆成绩;观测海马CA1区锥体细胞及顶树突,透射电镜观察其超微结构.结果:模型组学习和记忆成绩降低(P＜0.05),且海马CA1区锥体细胞数目也降低(P＜0.05),其顶树突总长度显著...     

槟榔碱提神效果及急性毒性作用研究

目的研究槟榔主要活性物质槟榔碱的提神及急性毒性作用,为槟榔食用安全提供参考依据。方法将昆明小鼠随机分成3组．腹腔注射各浓度的槟榔碱溶液30s后再注射苯巴比妥钠溶液,记录小鼠抗睡眠时间,同时以无菌生理盐水及同浓度的天竺葵作对照。采用霍恩法进行槟榔碱的急性毒性试验,计算其LD50并判定其毒性等级;解剖中毒小鼠,观察其病理变化。结果槟榔碱的抗睡眠时间随浓度的增大而增长,0．5mg的槟榔碱抗1．5×10^-4g苯巴比妥钠溶液引起的睡眠时间可达38min;槟榔碱的LD50是430mg／kg体重,95％可信限为295-626mg／kg体重,属于中等毒性。中毒死亡小鼠的肝脏稍微肿大,脾脏颜色变深、体积变大,肺部颜色略变深、有出血现象、肠内有空泡样。结论槟榔碱有抗苯巴比妥钠催眠的显著作用,是一种中等毒性物。     

烟碱诱导的海马脑片CA_1区长时程增强呈钙离子依赖性(英文)

目的:观察钙离子在烟碱诱导的大鼠海马脑片CA_1区长时程增强中的作用。方法:细胞外记录离体海马脑片CA_1区锥体细胞层群体峰电位。结果:至少烟碱1μmol·L~(-1)可诱导海马CA_1区长时程增强形成。移去脑脊液中的钙离子,烟碱不能诱导CA_1区长时程增强形成。硝苯地平1与10μmol·L~(-1)部分抑制而Tharpsigargin 1与10μmol·L~(-1)完全抑制烟碱诱导的长时程增强形成。结论:烟碱诱导的海马CA_1区长时程增强呈钙离子依赖性,胞外钙内流和胞内钙释放都参与了长时程增强形成。     

烟碱在大鼠海马诱导LTP的作用

目的　观察了烟碱在大鼠海马诱导长时程增强（ＬＴＰ） 的作用。方法　采用大鼠海马离体脑片灌流技术。结果　烟碱在大鼠海马ＣＡ１ 区可以诱发ＬＴＰ的作用;六烃季氨（Ｃ６） 可以阻断烟碱诱导ＬＴＰ;Ａｔｒｏｐｉｎｅ 对烟碱诱导ＬＴＰ作用无明显影响。无论在强直刺激前或后加入烟碱, 烟碱均可以易化强直刺激诱导ＬＴＰ的效应。结论　在大鼠海马ＣＡ１ 区烟碱可直接诱导ＬＴＰ,该作用由烟碱受体介导。烟碱可易化强直刺激诱导ＬＴＰ作用,提示两者诱导海马ＬＴＰ 的机制并不相同     

The action of thallium on the excitability of CA1 pyramidal cells in hippocampal slices

The effect of thallium ions on central neuronal activity was investigated in hippocampal slice preparations from guinea pigs and rats using extra- and intracellular recording techniques. Thallium induced a reversible and concentration-dependent reduction of the orthodromically evoked compound action potential of CA1 pyramidal cells with only weak effects on either afferent fiber activity, postsynaptic potentials or antidromically evoked responses. The membrane potential and input resistance of the pyramidal cells were not impaired by thallium. In contrast, variations in the maintained spike activity and spontaneously occurring inhibitory postsynaptic potentials were observed. It is concluded, that in contrast to its presynaptic action in the peripheral nervous system, thallium has a predominant postsynaptic target site in the hippocampal slice preparation. It is suggested that the neurotoxic action of thallium is not mediated by an interaction with specific ion channels of the cell membrane, but rather by an unspecific influence on the intracellular metabolism of the CA1 pyramidal cell.     

烟碱和槟榔碱对大鼠颌下腺肌醇含量的影响

急性实验中，间隔5 min反复ip N受体激动剂烟碱0.5, 1.0, 1.0, 2.0, 2.0 mg·kg^-1可显著提高大鼠颌下腺中肌醇含量，并为N受体拮抗剂美加明1.0 mg·kg^-1对抗，为肌醇磷酸酶抑制剂氯化锂69.4 mg·kg^-1 ip翻转；一次性ip M受体激动剂槟榔碱200 mg·kg^-1也可显著提高颌下腺肌醇含量，并为M受体拮抗剂阿托品2.0 mg·kg^-1对抗；反复注射烟碱后，再ip不影响肌醇含量的槟榔碱50 mg·kg^-1，两者产生协同效应，进一步提高肌醇含量. 慢性实验中，每日2次sc烟碱2.0-5.0 mg·kg^-1或槟榔碱2.0-10.0 mg·kg^-1 14 d后，均可使大鼠颌下腺中肌醇含量显著降低.     

烟碱与强直刺激诱导大鼠海马CA1区的长时程增强具有不同机制(英文)

目的:研究烟碱与强直刺激在海马CA1区诱导的长时程增强是否具有不同机制。方法:细胞外记录离体海马脑片CA1区锥体细胞层群体峰电位。结果:烟碱10μmol/L可易化强直刺激诱导的长时程增强,同样,强直刺激也可易化烟碱10μmol/L诱导的长时程增强。MK-801 10μmol/L或N~Gnitro-L-arginine methyl ester(L-NAME)20μmol/L可阻断强直刺激诱导的长时程增强,但不能抑制烟碱10μmol/L诱导的长时程增强。结论:烟碱与强直刺激在海马CA1区诱导的长时程增强具有不同的突触机制。     

Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices

1. The present study investigated the electrophysiological effects of songorine (1–100 μM), an alkaloid occurring in plants of the Aconitum genus, in rat hippocampal slices.
2. Songorine (10–100 μM) evoked a concentration-dependent increase in the amplitude of the orthodromic population spike and in the slope of the field e.p.s.p. The enhancement was long-lasting and was not reversed by up to 90 min of washout. Songorine failed to affect size and shape of the presynaptic fiber spike which represents the compound action potential of the Schaffer collaterals. This indicates that enhancement of the synaptic response is no consequence of an increased afferent excitability.
3. The antidromically evoked population spike was not affected by songorine at concentrations up to 100 μM suggesting that the enhancement of the orthodromic population spike and of the field e.p.s.p. was not due to an increase in pyramidal cell excitability.
4. The input-output curve for the postsynaptic population spike was shifted to the left implying that a presynaptic fiber spike of the same size elicited a larger postsynaptic response, indicating a decrease in threshold for generation of the population spike.
5. The songorine-evoked increase in excitability was not affected by the NMDA receptor antagonist, D-AP5. However, the effect of songorine was completely abolished by the selective dopamine D₂ receptor antagonist sulpiride (0.1 μM) as well as by haloperidol (10 μM) and was mimicked by application of the dopamine releaser, amantadine (100 mM). In contrast, the selective D₁ receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, did not block the action of songorine.
6. The results indicate that the plant alkaloid songorine enhances excitatory synaptic transmission which may be due to an agonistic action at D₂ receptors.

     

在烟碱诱导的大鼠海马CA1区长时程增强形成中p42/44促细胞分裂剂活化的蛋白激酶通路被激活

目的：研究p42/44 MAPK通路在烟碱诱导大鼠海马CA1区长时程增强（LTP）形成中的作用。方法：细胞外场电位启示离体海马脑片CA1区锥体细胞层群体峰电位;蛋白质印迹检测p42/44 MAPK磷酸化程度及其总蛋白表达。结果：PD98059 25μmol/L和50μmol/L呈剂量依赖性抑制烟碱（10μmol/L）诱导大鼠海马CA1区LTP的形成;在烟碱诱导LTP形成的海马CA1区组织内p42和p44 MAPK磷酸化均明显增强并有p42和p44 MAPK总蛋白表达量的增加。结论：p42/44 MAPK通路参与烟碱诱导大鼠海马CA1区LTP形成的信号转导过程。     

Effects of ethanol, arecoline, atropine and nicotine, alone and in various combinations, on rat cerebellar cyclic guanosine 3',5-monophosphate.

Rat cerebellar cyclic guanosine 3′,5′-monophosphate (cGMP) concentrations were determined by radioimmune methods after sacrifice with focused microwave fixation in animals pretreated with ethanol, arecoline, atropine and nicotine alone and in various combinations. Although arecoline and nicotine treatments resulted in large cerebellar increases in cGMP, they failed to antagonize ethanol's depressive effects. Atropine treatment did not augment ethanol-induced decreases in cGMP content. These data suggest that ethanol's depressant actions on cerebellar cGMP are independent of cholinergic mechanisms.     

The protein kinase C inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) disinhibits CA1 pyramidal cells in rat hippocampal slices.

1. The effects of the protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) on evoked synaptic potentials were investigated in the CA1 region of rat hippocampal slices by use of extracellular and intracellular recording techniques. 2. Extracellular recordings showed that superfusion with H-7 (10-100 microM) increased the amplitude of the population spike and the initial slope of the dendritic field e.p.s.p. H-7 also produced the appearance of multiple population spikes in the somatic region and in the dendritic field e.p.s.p. 3. H-7 (30 microM) induced the disappearance of intracellularly recorded inhibitory potentials elicited by orthodromic stimulation of CA1 pyramidal cells. At this concentration H-7 had no effect on resting membrane potential, input membrane resistance, and spike threshold. In voltage-clamped neurones H-7 blocked the antidromically evoked inhibitory currents and the spontaneous miniature inhibitory currents. 4. The hyperpolarizing effect of bath applied gamma-aminobutyric acid (GABA, 500 microM) or isoguvacine (30 microM) was not affected by 30 microM H-7. 5. Neither the PKC activity regulator sphingosine (10-40 microM) nor the H-7 analogue N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA-1004, 20-50 microM) which is devoid of activity on PKC at these concentrations, affected the extracellularly recorded dendritic field e.p.s.p. or population spike. 6. It is concluded that the disinhibitory effect produced by H-7 is due to the block of a H-7-sensitive PKC which is involved in the spontaneous and evoked release of GABA.