摘要
目的：在参照大量文献的基础上进行动物实验以确定7日龄SD大鼠氯胺酮的亚麻醉剂量,并进行正常成年大鼠在体海马区长时程增强的诱发。
方法：前一部分应用7日龄SD大鼠20只,雌雄各半,被随机分成4组：氯胺酮组分别腹腔注射25、50、1OOmg/kg氯胺酮(分别以生理盐水稀释到0.2m1),并标以K1、K2、K3组；对照组给予等量的生理盐水。注射后10分钟用lml皮试针经左心室采0.2mI血进行血气分析,记录麻醉后三天各组幼鼠的体重。后一部分应用成年SD大鼠6只,经20%乌拉坦麻醉成功后,将头部固定于立体定位仪上,进行在体海马区长时程增强的诱发。
结果：K3组大鼠经腹腔注射氯胺酮后,很快出现明显的呼吸抑制；K1组和K2组血气分析结果与对照组相比无统计学差异(P>0.05),三组大鼠体重增长无统计学差异(P>0.05)。正常成年大鼠在体海马区LTP诱发成功且稳定。
结论：25mg/kg和50mg/kg氯胺酮麻醉不影响7日龄SD大鼠血气分析结果及体重的增长；通过本实验设计及方法可准确定位海马相应区域并可稳定诱发在体海马区长时程增强。
目的：观察单次侧脑室注射氯胺酮短时间是否对海马区神经纤维突触可塑性造成影响。
方法：成年SD大鼠12只,重量在250g左右,雌雄各半,随机分为实验组(C-I组)和对照组(C组)。经20%乌拉坦麻醉后,在立体定位仪的指引下分别从大鼠右侧脑室注射51μl的生理盐水和50μg的氯胺酮(生理盐水稀释至5μl),然后记录在体海马区长时程增强。
结果：高频刺激后,C组PS幅值维持在较高水平：刺激后30min时为条件刺激PS幅值的(216.29±12.11)%(n=8),刺激后60min时为(202.33±11.53)%(n=8)；C-I组PS幅值在高频刺激后前5min较高,后随着时间增加有大幅减小,刺激后30min时为条件刺激PS幅值的(138.04±6.50)%(n=9),刺激后60min时为(149.60±10.86)%(n=9),C-I组LTP突触可塑性改变程度较对照组显著降低(P<0.05)。
结论：成年SD大鼠侧脑室单次注射常规剂量的氯胺酮后短时间内即可显著抑制海马区神经元的突触传递可塑性。
目的：单次给予7日龄SD大鼠不同剂量的氯胺酮麻醉,研究其成年后水迷宫和在体海马区LTP的变化。
方法：7日龄SD大鼠30只,雌雄各半,随机分为氯胺酮深麻醉组(K1组)、氯胺酮浅麻醉组(K0.5组)和对照组(C组)。K1组、K0.5组分别腹腔注射50mg/kg和25mg/kg(分别以生理盐水稀释到0.2ml)的氯胺酮实施麻醉。C组腹腔注射0.2ml的生理盐水。2.5月龄时,进行水迷宫实验检测大鼠空间学习记忆能力。一周后,在大鼠双侧海马进行LTP诱发。
结果：三组水迷宫实验中逃避潜伏期、平均游泳距离和平均游泳速度均无显著性差异(P>0.05)。在体海马区长时程增强诱发实验中,两个氯胺酮实验组较对照组均可明显降低海马LTP水平(P<0.05),但K1和K0.5组降低海马LTP程度无显著性差(P>0.05)。
结论：幼鼠氯胺酮麻醉不影响其成年后空间学习记忆能力,但可降低海马突出可塑性,且不同深度麻醉对成年后学习记忆功能的影响一致。
Objective:To determine sub-anesthetic dose of ketamine for7days old SD rats on the basis of animal experiments and literature search. And to induce long-term potentiation in hippocampus of normal adult rats in vivo.
Methods:20SD rats of7days old were used in the first part, half male and half female. They were divided into four groups:group C, K1, K2, K3, which was injected with0.2ml NS or25,50,100mg/kg ketamine (diluted to0.2ml with NS).0.2ml blood was extracted from left ventricular for blood-gas analysis10min later. Body weight of each rat was recorded for three days.6adult SD rats were used in the other part. After being anesthetized with20%Urethane, each rat was fixed in stereotaxic apparatus and long-term potentiation was induced on hippocampus.
Results:After ketamine being injected, rats of group K3appeared respiratory depression quickly. Results of blood-gas analysis were no significant difference among group Kl, K2and C (P>0.05), also as weight (P>0.05). Induction of LTP on hippocampus of normal adult rats was successful and stable.
Conclusion:It didn't affect the result of blood-gas analysis and weight gain those rats of7days old were anesthetized with25mg/kg or50mg/kg ketamine. We could accurately locate the specified region on hippocampus and induce LTP on hippocampus of normal adult rats successfully and stably following our experimental method.
Objective: To observe the effect of ketamine of intracerebroventricular inject to adult SD rats on LTP of Hippocampus.
Methods:12Adult SD rats, weight about250g, half male and half female. They were randomly divided into group C and group C-I. After being successfully anesthetized by urethane, each rat was fixed on stereotaxic apparatus. LTP was recorded after intracerebroventricular injection of NS or ketamine (50μg)5μl respectively.
Results:30min after stimulation, PS amplitudes of group C and C-I were (216.29±12.11)%and (138.04±6.50)%(P<0.05).60min after stimulation, PS amplitudes were (202.33±11.53)%and (149.60±10.86)%(P<0.05). LTP of group C-I reduced obviously.
Conclusion:Ketamine of intracerebroventricular injection to adult SD rats can reduce synaptic plasticity of hippocampus.
Objective: To observe the effect of single ketamine anesthesia for neonate on MWM and LTP of adult SD rats.
Methods:30seven days old SD rats were divided into group C (NS0.2ml, ip.), group K1(ketamine50mg/kg, ip.) and group K0.5(ketamine25mg/kg, ip.). MWM and hippocampal LTP were recorded respectively at rats2.5months old and one week later.
Results:In MWM, three groups showed no significant difference (P>0.05). In LTP, group K1and K0.5showed significant lower compared with group C (P<0.05), but no significant difference between them (P>0.05).
Conclusion:Single ketamine anesthesia for neonate reduced synaptic plasticity of adult SD rats, but didn't affect spatial learning and memory. And light and deep anesthesia had the same effect on degree of inhibiton to synaptic plasticity.
引文
[1]林林,黄陈平,方周溪等.多次氯胺酮麻醉对大鼠学习记忆的影响[J].安徽医药,2006,10(7)：490-491.
[2]Orser BA, Pennefather PS, MacDonald JF. Multiple mechanism s of ketamine blockade of N-methyl D-aspartate receptors [J]. Anesthesiology,1997,86(4): 903-917.
[3]Lu Y, Christian K, Lu B. BDNF:A key regulator for protein synthesis dependent LTP and long term memory [J]? Neurobiol Learn Mem,2008,89(3):312-323
[4]倪锦.氯胺酮对乳鼠脑皮质神经细胞凋亡的影响机制探讨及参附注射液的防治[D].广州：南方医科大学,2011：
[5]Peng S, Zhang Y, Wang H, et al. Anesthetic ketamine counteracts repetitive mechanical stress-induced learning and memory impairment in developing mice [J]. Mol Biol Rep,2011,38(7):4347-4351.
[6]Tan S, Rudd JA, Yew DT. Gene expression changes in GABA(A) receptors and cognition following chronic ketamine administration in mice [J]. PLoS One,2011, 6(6):e21328.
[7]Shi Q, Guo L, Patterson TA, et al. Gene expression profiling in the developing rat brain exposed to ketamine [J]. Neuroscience,2010,166(3):852-863.
[8]Soriano SG, Liu Q, Li J, et al.Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain [J]. Anesthesiology,2010,112(5):1155-1163.
[9]Ibla JC, Hayashi H, Bajic D, et al. Prolonged exposure to ketamine increases brain derived neurotrophic factor levels in developing rat brains [J]. Curr Drug Saf,2009, 4(1):11-16.
[10]Slikker WJ, Zou X, Hotchkiss CE, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey [J]. Toxicol Sci,2007,98(1):145-158.
[11]Zou X, Patterson TA, Divine RL, et al. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain [J]. Int J Dev Neurosci,2009, 27(7):727-731.
[12]Liu F, Paule MQ Ali S, et al. Ketamine-induced neurotoxicity and changes in gene expression in the developing rat brain [J]. Curr Neuropharmacol,2011, 9(1):256-261.
[13]Zou X, Patterson TA, Sadovova N, et al. Potential neurotoxicity of ketamine in the developing rat brain [J]. Toxicol Sci,2009,108(1):149-158.
[14]Fredriksson A, Ponten E, Gordh T, et al. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits [J]. Anesthesiology,2007,107(3):427-436.
[15]Young C, Jevtovic-Todorovic V, Qin YQ, et al. Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain [J]. Br J Pharmacol,2005,146(2):189-197.
[16]张建楠.氯胺酮对未成年大鼠学习记忆和细胞外信号调节激酶表达的影响[D].苏州：苏州大学,2008：
[17]韩太真,吴馥梅.学习与记忆的神经生物学[M].北京：北京医科学大学中国协和医科大学联合出版社,1998：162-176.
[18]吴俊芳,刘态.现代神经科学研究方法[M].北京：中国协和医科大学出版社,2005：644-661.
[19]Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits [J]. J Neurosci,2003,23(3):876-882.
[20]Hayashi H, Dikkes P, Soriano SG. Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain [J]. Paediatr Anaesth,2002, 12(9):770-774.
[21]Soriano SG, Liu Q, Li J, et al. Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain [J]. Anesthesiology,2010,112(5):1155-1163.
[22]黄冰,张云龙.氯胺酮的研究进展[J].《国外医学》麻醉学与复苏分册,2000,21(5)：306-308.
[23]Abe K, Fujimoto T, Akaishi T, et al. Basolateral amygdala D1- and D2-dopaminergic system promotes the formation of long-term potentiation in the dentate gyrus of anesthetized rats [J]. Prog Neuropsychopharmacol Biol Psychiatry, 2009,33(3):552-556.
[24]谭涛,张保良,田心.寡聚体Aβ1-42对大鼠海马突触可塑性的慢性影响[J]. 生理学报,2011,63(3)：225-232.
[25]李钢,罗佛全,赵为禄.氯胺酮对SD大鼠后代学习记忆功能影响的实验研究[J].实用临床医学,2009,10(5)：4-6.
[26]Nayar R, Sahajanand H. Does anesthetic induction for Cesarean section with a combination of ketamine and thiopentone confer any benefits over thiopentone or ketamine alone? A prospective randomized study [J]. Minerva Anestesiol,2009, 75(4):185-190.
[27]Sigtermans M, Dahan A, Mooren R, et al. S(+)-ketamine effect on experimental pain and cardiac output: a population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers [J]. Anesthesiology,2009,111 (4):892-903.
[28]曲强.氯胺酮对SD幼鼠学习记忆和认知功能的影响[D].锦州：辽宁医学院,2011：
[29]Ikonomidou C, Olney JW. Neurotransmitters and apoptosis in the developing brain [J]. Biochem Pharmacol,2001,62(7):401-405.
[30]Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly [J]. Best Pract Res Clin Anaesthesiol,2003,17(2):259-272.
[31]Ge ZJ, Wu WQ, Ju G, et al. Modulatory role of intrathecal administration of nocistatin on protein kinase C dependent phosphorylations of the spinal cord PKCa and NMDA receptor subunit NRla induced by formaldehyde in rat [J]. Chin Pharmacol Bull,2010,26(5):693-694.
[32]Takai H, Katayama H, Uetsuka K, et al. Distribution of N-methyl-D-aspartate receptors in the developing rat brain [J]. Exp Mol Pathol,2003,75(1):89-94.
[33]Sepulveda J, Oliva P, Contrerm E. Neurochemical changes of the extra-cellular concentrations of glutamate and aspartate in the nucleus accumbens of rats after chronic administration of morphine[J]. Eur J Phannacol,2004,483(3):249-258.
[34]Bleiberg AH, Salvaggio CA, Roy LC, et al. Low-dose ketamine:Efficacy in pediatric sedation [J]. Pediatr Emerg Care,2007,23(3):158-162.
[35]Rana A, Hallaq A. Association of NR3A with the NMDAR NR1 and NR2 Subunites [J].MoI Pharmacol,2002,62(5):1119-1127.
[36]Vissel, Krupp JJ, Heinemann FA. Use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux [J]. Nat Neurosci,2001,4(6):587-596.
[37]Donald W, Ki YJ. In vivo blockade of NMDA receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex [J]. Neuroscience,2003,121(3):51-63.
[38]Dallimore D, Anderson BJ, Short TG, et al. Ketamine anesthesia in children-exploring infusion regimens [J]. Pediatr Anesth,2008,18(8):708-714.
[39]Floyd DW, Jung KY, McCool BA. Chronic ethanol ingestion facilitates NMDA receptor function and expression in rat lateral/basolateral amygdala Neurons [J]. J Pharmacol Exp Ther,2003,307(3):1020-1029.
[40]Chiye A, Fujisawa S, Mahadomrongkul V. NMDA receptor blockade in intact adult cortex increases trafficking of NR2A subunits into spines, postsynaptic densities and axon terminals[J].Brain Research,2003,963(9):139-149.
[41]Komai S, Licznerski P, Cetin A, et al. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development [J]. Nat Neurosci,2006,9(9):1125-1133.
[42]Tovar KR, Westbrook GL. Mobile NMDA receptors at hippocampal synapses [J].Neuron,2002,34(2):255-264.
[43]徐小林,文静,戴体俊,等.多次使用氯胺酮对小鼠体重、自主活动和学习记忆的影响[J].徐州医学院学报,2008,28(4)：257-260.
[44]吕春燕,马跃荣.小鼠心脏穿刺采血并存活的几点注意事项[J].泸州医学院学报,2006,29(3)：206
[45]刘毓和,吴新民,杜敏逸.咪哇安定、异丙酚和氯胺酮对老年大鼠认知功能的影响[J].中华麻醉学杂志,2006,26(4)：315-317.
[46]Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome [J]. Science,2000,287(5455): 1056-1060.
[47]Slikker W Jr, Paule MG, Wright LKM, et al. Systems biology approaches for toxicology [J]. J Appl Toxicol,2007,27(3):201-217.
[48]Farber NB, Olney JW. Drugs of abuse that cause developing neurons to commit suicide [J]. Brain Res Dev Brain Res,2003,147(1-2):37-45.
[49]Scallet AC, Schmued LC, Slikker WJ, et al. Developmental neurotoxicity of ketamine:morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons[J]. Toxicol Sci,2004,81(2):364-370.
[50]饶子亮,倪锦,钟志勇,等.氯胺酮麻醉对乳鼠脑细胞凋亡的影响[J].中国比较医学杂志,2010,20(9)：37-40.
[51]林也容,黄晶,李娟,等.氯胺酮对培养胎鼠皮层神经元NMDA兴奋毒性损伤的保护[J].临床和实验医学杂志,2011,10(11)：801-808.
[52]Himmelseher S, Durieux ME. Revising a dogma:ketamine for patients with neurological injury [J]? Anesth Analg,2005,101(2):524-534.
[53]谢凌燕,戴泽平,谭永胜.氯胺酮对幼龄大鼠大脑淀粉样前体蛋白mRNA表达的影响[J].皖南医学院学报,2010,29(1)：8-12.
[54]李钢.孕期接受氯胺酮麻醉对SD大鼠后代学习记忆功能的影响[D].南昌：南昌大学医学院,2009：
[55]武云飞,王志萍,江山,等.多次氯胺酮麻醉对发育早期大鼠空间辨别学习记忆与海马CA1区突触长时程增强的影响[J].徐州医学院学报,2005,25(3)：221-224.
[56]Scallet AC, Schmued LC, Slikker W Jr, et al. Developmental neurotoxicity of ketamine:morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons[J]. Toxicol Sci,2004,81(2):364-370.
[57]王贤裕,田玉科.腹腔重复注射小剂量氯胺酮术后镇痛对趾部切口术大鼠认知功能的影响[J].中华麻醉学杂志,2005,25(3)：205-207.
[58]Bhutta AT. Ketamine:a controversial drug for neonates [J]. Semin Perinatol, 2007,31(5):303-308.
[59]Kozek-Langenecker SA, Marhofer P, Sator-Katzenschlager SM, et al. S(+)-ketamine for long-term sedation in a child with retinoblastoma undergoing interstitial brachytherapy [J]. Pediatr Anesth,2005,15(3):248-250.
[60]Morgan CJ, Riccelli M, Maitland CH, et al. Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users [J]. Drug Alcohol Depend,2004,75(3):301-308.
[61]蒯建科,孙绪德,高昌俊,等.氯胺酮对新生大鼠认知功能和海马突触素表达的影响[J].医学研究生学报,2008,21(4)：364-367.
[62]李艳,廖艺聪,赵冰雪,等.昂丹司琼对氯胺酮麻醉小鼠学习记忆功能的影响[J].江苏医药,2011,37(12)：1388-1390.
[63]李爽,万佳,陈文捷.心脑佳配方对慢性酒精中毒大鼠学习记忆及海马NMDA受体亚基NR2B表达的影响[J].中国应用生理学杂志,2011,27(1)：5-7.
[64]董晓华,张丹参,孟宪勇.Glu/GABA水平相关性对学习记忆的影响[J].中国老年学杂志,2006,68(2)：283-285.
[65]曲强,焦金菊,林宇涵,等.不同剂量氯胺酮对SD幼鼠学习记忆及认知功能的影响[J].中国医学工程,2011,19(1)：97-100.
[66]Shu Y. Neuronal signaling in central nervous system [J]. Acta Physiologica Sinica,2011,63(1):1-8.
[67]Kole MH, Letzkus JJ, Stuart GJ. Axon initial segment Kv1 channels control axonal action potential waveform and synapticefficacy [J].Neuron,2007,55(4): 633-647.
[68]Komai S, Licznerski P, Cetin A, et al. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development [J]. Nat Neurosci,2006,9(9):1125-1133.
[69]张向阳,刘玉庆,孔庆胜.大鼠学习记忆能力与特定脑区某些氨基酸含量的相关性[J].中国行为医学利·学,2005,14(1)：158-159.
[70]Lupien SJ, Maheu F, Tu M, et al. The effect s of stress and stress hormones on human cognition Implications for the field of brain and cognition [J]. Brain Cogn, 2007,65(8):209-237.
[71]杜鹃,王红伟.侧脑室注射氯胺酮对大鼠学习能力的影响[J].医药论坛杂志,2009,30(23)：12-13.
[72]王志萍,武云飞,江山,等.多次氯胺酮给药对大鼠海马CA1区突触长时程增强的影响[J].中华麻醉学杂志,2006,26(4)：309-311.
[73]吴俊芳,刘吝.现代神经科学研究方法[M].北京：中国协和医科大学出版社,2005：696-698.
[74]Morris RGM, Garrud P, Rawlins JNP, et al. Place navigation impaired in rats with hippocampal-lesions[J]. Nature,1982,297(5868):681-683.
[75]陈远寿,罗孝美,陈旻,等NVP-AAM077和Ro25-6981对全脑缺血小鼠海马神经元损伤及BDNF表达的影响[J].中国药理学通报,2010,26(8)：1010-1013.
[76]刘梅,郑素军,董蕾,等.侧脑室注入胃动素对大鼠摄食及学习记忆能力的影响[J].西安交通大学学报(医学版),2011,32(1)：43-46.
[77]李国彰.神经生理学[M].北京：人民卫生出版社.2007：450-451.
[78]周晓林,张进,王丹东,等.莨菪碱与氯胺酮合用对小鼠学习记忆的影响[J].徐州医学院学报,2006,26(2)：137-139.
[79]赵梅兰,马强,曹晓哲,等.电磁脉冲对大鼠学习记忆能力和长时程增强的影响[J].中华物理医学与康复杂志,2001,23(2)：69-71.
[80]冯春生,王金,岳云,等.氯胺酮对大鼠海马脑片突触长时程增强效应的影响[J].吉林大学学报(医学版),2008,34(5)：746-750.
[81]林蕾,张良成,郭永正.氯胺酮合用盐酸戊乙奎醚对新生大鼠突触素表达的影响[J].中国当代儿科杂志,2010,12(1)：51-55.
[82]Fredriksson A, Archer T, Alm H, et al. Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration[J]. Behav Brain Res,2004, 153(2):367-376.
[83]Wang C, Sadovova N, Hotchkiss C, et al. Blockade of N-methyl-Daspartate receptors by ketamine produces loss of postnatal day 3 monkey frontal cortical neurons in culture[J]. Toxicol Sci,2006,91(1):192-201.
[84]Wang C, Sadovova N, Fu X, et al. The role of NMDA receptors in ketamine-induced apoptosis in rat forebrain culture [J]. Neuroscience,2005,132: 967-977.
[85]Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain [J]. Science,1999, 283(5398):70-74.
[86]Clancy B, Finlay BL, Darlington RB, et al. Extrapolating brain development from experimental species to humans [J]. Neurotoxicology,2007,28(5):931-937.
[87]Stratmann G, Sall JW, May LD, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats [J]. Anesthesiology,2009,110(4):834-848.
[88]Ghoneim MM. Drugs and human memory (part 1):Clinical, theoretical, and methodologic issues [J].Anesthesiology,2004,100(4):987-1002.
[1]Bliss TV, Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path [J]. J Physiol,1973,232(2):331-356.
[2]Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus [J]. Nature,1993,361(6407):31-39.
[3]吴俊芳,刘志.现代神经科学研究方法[M].北京：中国协和医科大学出版社,2005：
[4]韩太真.突触可塑性与长时程增强现象的研究进展[J].西安交通大学学报,2005,26(4)：305-308.
[5]Lynch MA. Long-term potentiation and memory [J]. Physiol Rev,2004, 84(1):87-136.
[6]许琳,张均田.突触长时程增强形成机制的研究进展[J].生理科学进展,2001,32(4)：298-301.
[7]陈玲.长时程增强分子机制的研究进展[J].国际神经病学神经外科学杂志,2006,33(6)：537-539.
[8]Cormier RJ, Greenwood AC and Connor JA. Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold [J]. J Neurophysiol,2001,85(1):399-406.
[9]Sheng M, Kim MJ. Postsynaptic signaling and plasticity mechanisms [J]. Science, 2002,298(5594):776-780.
[10]Luscher C, Nicoll RA, Malenka RC, et al. Synaptic plasticity and dynamic modulation of the postsynaptic membrane [J]. Nat Neurosci,2000,3(6):545-550.
[11]Li L, Chin LS. The molecular machinery of synaptic vesicle exocytosis[J]. Cell Mol Life Sci,2003,60(5):942-960.
[12]Xiao MY, Wasling P, Hanse E, et al. Creation of AMPA-silent synapses in t he neonatal hippocampus [J]. Nat Neurosci,2004,7(3):236-243.
[13]Abraham WC, Williams JM. Properties and mechanisms of LTP maintenance [J]. Neuroscientist,2003,9 (6):463-474.
[14]Carroll RC, Beattie EC, von Zastrow M, et al. Role of AMPA receptor endocytosis in synaptic plasticity [J]. Nat Rev Neurosci,2001,2(5):315-324.
[15]姚利君,周苏娅,夏强.代谢型谷氨酸受体在突触可塑性中的作用研究进展[J].生理科学进展,2004,35(1)：73-76.
[16]Park M, Penick EC, Edwards JQ et al. Recycling endosomes supply AMPA receptors for LTP [J]. Science,2004,305(5692):1972-1975.
[17]Emptage NJ, Reid CA, Fine A, et al. Optical quantal analysis reveals a presynaptic component of LTP a hippocampal Schaffer-associational synapses [J]. Neuron,2003,38(5):797-804.
[18]郑小波,田心,宋毅军.在脑片水平上突触可塑性长时程增强的研究进展[J].国际生物医学工程杂志,2008,31(2)：85-88.
[19]吕和平,任爱红,武晓洛,等.海马在学习记忆中的作用研究进展[J].洛阳医专学报,2002,20(4)：354-355.
[20]Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory:an evaluation of the hypothesis [J]. Annu Rev Neurosci,2000,23:649-711.
[21]Pang PT, Lu B. Regulation of late-phase LTP and long-term memory in normal and aging hippocampus:role of secreted proteins tPA and BDNF [J]. Ageing Res Rev,2004,3(4):407-430.
[22]向小军,李凌江,郝伟.长时程增强与应激、药物依赖的关系[J].中国行为医学科学,2002,11(5)：597-598.
[23]Wang J, Akirav I, Richter-Levin G. Short-term behavioral and electrophysiological consequences of underwater trauma [J]. Physiol Behav, 2000,70(3-4):327-332.
[24]郑晖,杨权,许崇涛,等.慢性应激对大鼠海马CA1区长时程增强的影响及苯妥英钠的效应[J].中国神经精神疾病杂志,2004,30(4)：290-291.
[25]刘媛媛,闵苏.长时程增强及长时程抑制与全麻药关系的研究进展[J].国际麻醉学与复苏杂志,2009,30(6)：548—550.
[26]Barr G, Anderson BE, Owall A, et al. Being awake intermittently during propofol-induced hypnosis:a study of BIS, explicit and implicit memory [J]. Acta Anaesthesiol Scand,2001,45(7):834-838.
[27]Wei H, Xiong W, Yang S, et al. Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats [J]. Neurosci Lett,2002,324(3):181-184.
[28]Nagashima K, Zommski CF, Izumi Y. Propofol inhibits long-term potentiation but not long-term depression in rat hippocampal slices [J]. Anesthesiology,2005, 103(2):318-326.
[29]Takamatsu I, Sekiguehi M, Wada K, et al. Propofol-mediated impairment of CA1 long-term potentiation in mouse hippocampal slices [J]. Neurosci Lett,2005, 389(3):129-132.
[30]Kozinn J, Mao L, Arora A, et al. Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol [J]. Anesthesiology,2006,105(6):1182-1191.
[31]Vinson DR, Bradbury DR. Etomidate for procedural sedation in emergency medicine [J]. Ann Emerg Med,2002,39(6):592-598.
[32]Simon W, Hapfelmeier G, Kochs E, et al. Isoflurane blocks synaptic plasticity in the mouse hippocampus [J]. Anesthesiology,2001,94(6):1058-1065.
[33]Ishizeki J, Nishikawa K, Kubo K, et al. Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms [J]. Anesthesiology,2008, 108(3):447-456.
[34]Naruo H, Onizuka S, Prinee D, et al. Sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term potentiation [J]. Anesthesiology,2005,102(5):920-928.
[35]Ji RR, Kohno T, Moore KA, et al. Central sensitization and LTP:Do pain and memory share similar mechanisms [J]? Trends Neurosci,2003,26(12):696-705.
[36]Sandkahler J. Learning and memory in pain pathways [J]. Pain,2000,88(2): 113-118.
[37]Klein T, Magerl W, Nickel U, et al. Effects of the NMDA-receptor antagonist ketamine on perceptual correlates of long-term potentiation within the nociceptive system [J]. Neuropharmacology,2007,52(2):655-661.
[38]Benrath J, Brechtel C, Stark J, et al. Low dose of S+-ketamine prevents long-term potentiation in pain pathways under strong opioid analgesia in the rat spinal cord in vivo [J]. Br J Anaesth,2005,95(4):518-523.
[39]Hu XD, Ge YX, Hu NW, et al. Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats [J]. Neuropharmacology,2006,50(2):238-244.
[40]Cheng G, Kendig JJ. Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAa or glycine receptors [J]. Anesthesiology,2000,93(4):1075-1084.
[41]Pang PT, Teng HK, Zaitsev E, et al. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity [J]. Science,2004,306(5695): 487-491.
[42]秦锦标,周红.脑源性神经营养因子在长时程增强中的作用[J].东南大学学报,2007,26(5)：389-393.
[43]左听,邱太兴,潘奇波,等.脑源性神经营养因子在学习记忆中作用机制的研究进展[J].海军医学杂志,2009,30(3)：271-273.
[44]Murer M, Yan Q, Raisman-Voiaii R. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease[J].Prog Neurobiol,2001,63(1):71-124.
[45]Thomas K, Davies A. Neurotrophins:a ticket to ride for BDNF [J]. Curt Bid, 2005,15(7):262-264.
[46]Dawson NM, Hamid EH, Egan MF, et al. Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment [J]. Synapse,2001,39(1):70-81.
[47]刘佩,刘喆.脑源性神经营养因子在海马学习记忆中的作用[J].长春中医药大学学报,2009,25(2)：195-196.
[48]Zhou Q, Poo MM. Reversal and consolidation of activity-in-duced synaptic modifications [J]. Trends Neurosci,2004,27:378-383.
[49]Hyman JM, Wyble BP, Goyal V, et al. Stimulation in hippocampal region CA1 in behaving rats yields long-term potentiation when delivered to the peak of theta and long-term depression when delivered to the trough [J]. J Neurosci,2003, 23(37):11725-11731.
[50]张莉,韩太真.长时程增强翻转的研究进展[J].生理学进展,2010, 41(4)：275-278.
[51]Zho WM, You JL, Huang CC, et al. The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine induces a novel form of depotentiation in the CA1 region of the hippocampus [J]. J Neurosci,2002,22(20):8838-8849.
[52]Lin HC, Wang SJ, Luo MZ, et al. Activation of group Ⅱ metabotropic glutamate receptors induces long-term depression of synaptic transmission in the rat amygdala [J]. J Neurosci,2000,20(24):9017-9024.
[53]Shi NN, Jiang ML, Zhang L, et al. Prolonged reversal of long-term potentiation that is N-methyl-D-aspartate receptor independent:implications for memory formation [J]. Curr Neurovasc Res,2008,5(1):52-59.
[54]Li R, Huang FS, Abbas AK, et al. Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity [J]. BMC Neurosci,2007,8:55.
[55]Zhang L, Meng K, Li YH, et al. NR2A-containing NMDA receptors are required for L-LTP induction and depotentiation in CAl region of hippocampal slices [J]. Eur J Neurosci,2009,29(11):2137-2144.
[56]Rex CS, Kramar EA, Colgin LL, et al. Long-term potentiation is impaired in middle-aged rats:Regional specificity and reversal by adenosine receptor antagonists [J]. J Neurosci,2005,25(25):5956-5966.