Facilitation and disruption of the long-term store of memory with neural excitants

Male hybrid mice (C57BL/6J × DBA/2J) were trained for 2 days in a 6-unit brightness discrimination maze. Beginning 24 hr after training, mice were administered daily injections of strychnine sulphate, Metrazol, d-amphetamine sulphate, caffeine citrate, nicotine alkaloid, or saline for 5 days. Forty-eight hr after the injection series was completed, mice were trained to criterion in the maze. Mice administered strychnine sulphate or Metrazol showed significantly better retention than those administered saline while mice administered d-amphetamine sulphate were significantly poorer. Nicotine alkaloid produced a trend toward facilitation, while caffeine citrate had no effect. The observed facilitation and disruption were not due to enhancement or impairment of learning ability and could not be attributed to effects upon the consolidation process.     

Nicotine and caffeine: Disruption of the long-term store of memory and proactive facilitation of learning in mice

The effects of nicotine and caffeine on the long-term store of memory in mice were determined for a wide range of dosages. Male F₁ mice (C57BL/6J×DBA/ 2J) were given two trials in an appetitive maze 24 h apart. Twenty-four hours after the second trial each animal was given the first of five daily injections of one of the dosages being tested. Beginning 48 h after the last injection, animals received one trial per day until a learning criterion was reached. Both nicotine and caffeine produced a dose-dependent disruption of performance in the trials following the injection series. In contrast, nicotine produced facilitation of performance in animals given a series of injections in the absence of previous training, and caffeine produced a strong trend in this direction. It was concluded that these drugs produced disruption of the long-term store of memory for the initial training and proactive facilitation of maze learning. The existence of separate and opposing effects of these drugs on different aspects of learning and memory was discussed.This investigation was supported by National Institute of Mental Health Grant MH20574 and National Institute of Mental Health Predoctoral Fellowship MH46975     

Dose-dependent effects of heroin on memory in two inbred strains of mice

Heroin was administered to DBA/2 and C57BL/6 mice, trained in the five-choice Yerkes-Thompson-Bryant-Bovet-Nitti apparatus for pattern discrimination, in two sets of experiments. In a first set, pretrial administrations of heroin (0.1, 0.25, or 0.5 mg/kg) improved performance in both strains. In a second set, heroin (0.5 mg/kg) immediately following each training session were followed by performance improvements in both strains, while the performance of C57 mice was improved and that of the DBA mice was impaired by 5 mg/kg of opiate. No effect was evident in this set of experiments when heroin was injected 2 h after each session, suggesting that effects of the pretrial treatments were due to influences of the opiate on the consolidation processes of the strains tested.     

d-Amphetamine effects on attention and memory in the albino and hooded rat

Albino and hooded rats were injected with either d-amp or physiological saline and tested on acquisition, reversal, and recall of a brightness discrimination. Hooded rats acquired and reversed the discrimination more quickly than albino rats. D-amp retarded both acquisition and reversal while enhancing recall. The results indicated that d-amp disrupts attention while enhancing memory. The systems which may mediate this behavioral fractionation are discussed.     

Strain-dependent effects of naloxone on discrimination learning in mice

The effects of post-trial naloxone administration were studied in two inbred strains of mice, C57BL/6 (C57) and DBA/2 (DBA), tested in two different experimental conditions. These were a Y-water maze (requiring escape from water) and the Yerkes — Thompson — Bovet-Nitti apparatus for pattern discrimination (requiring escape from electric shock). Two series of experiments were carried out. In the first series, naloxone improved acquisition in DBA and impaired acquisition in C57 mice either trained to swim towards the dark or to discriminate between oblique bars. Light-oriented behavior, perhaps due to non-conditioned tendencies, was improved in the Y-water maze following naloxone administration in both strains.     

Effects of chlorpromazine and imipramine on discrimination learning,consolidation, and learned behavior in two inbred strains of mice

Chlorpromazine and imipramine were administered to DBA/2J and C57BL/6J mice swimming in a Y water maze toward a light source (L Procedure, corresponding to innate tendency) or towards the dark (D Procedure, sorresponding to the acquisition of a new pattern of behavior). In two sets of experiments the drugs were administered to naive mice before and after each training session, respectively.In both strains, in the pretrial experiments, the innate tendencies were improved by both drugs; the acquisition of a new pattern of behavior was improved following imipramine but impaired following chlorpromazine. In the posttrial experiments (D procedure) the consolidation processes of both strains were improved following imipramine and impaired following chlorpromazine.In a third set of experiments imipramine was administered to previously trained mice of both strains and chlorpromazine to previously trained C57 mice. In both procedures the administration of increasing doses of both drugs was followed by a progressive lengthtening of the swimming times in the previously trained C57 mice; performance disruptions were evident in both procedures in trained DBA mice following imipramine.     

Facilitation of the long term memory store with strychnine: a reexamination.

Contrary to previous findings, some recent studies have reported that several daily injections of strychnine, beginning 24 hr after learning, facilitates subsequent retention. The present paper reports 3 studies using mice which suggest that strychnine has no effect on retention when the learning-injection interval is 24 hr. This absence of an effect was found using a range of strychnine doses. Furthermore, the absence of the facilitation effect was found not to be due to any failure of animals to learn prior to injection or to the fact that all animals performed asymptotically on the retention test.     

七氟醚麻醉对新生鼠学习与记忆的影响

目的 探索用七氟醚麻醉发育期小鼠是否会引起成长过程中学习记忆障碍。 方法 实验包括122只新生鼠(出生后7 d)。其中72只分别经七氟醚1.0或0.5最低肺泡有效浓度(minimum alveolar concentration,MAC)麻醉或吸入40% O₂ 2 h,4周或12周行水迷宫实验,记录训练各天潜伏期和游泳速度,以及探索期平台滞留时间和平台穿越次数。另外50只小鼠用于测定七氟醚麻醉(1.0或0.5 MAC)过程(0、1、2 h)中动脉血血气分析。 结果 新生鼠在整个麻醉过程中,pH值、PaCO₂、PaO₂和SaO₂均保持稳定,P>0.05。麻醉后4周,训练期后3 d,对照组小鼠潜伏期明显低于麻醉组,且后2 d,0.5 MAC组小鼠的潜伏期明显短于1.0 MAC组。探索期,对照组小鼠平台停留时间和平台穿越次数均明显高于2组麻醉组。麻醉后12周,1.0 MAC组小鼠在训练第5天潜伏期仍明显延长。探索期,对照组小鼠平台停留时间和(或)平台穿越次数均明显高于麻醉组。 结论 七氟醚麻醉引起新生鼠成长过程中学习与记忆障碍,其程度与药物浓度有关,且随时间推移减弱。     

Paradoxical sleep and memory: Long-term disruptive effects of anisomycin

The effects of the protein synthesis inhibitor Anisomycin (ANI) on Paradoxical Sleep (PS or REM sleep), slow wave sleep (SWS), and retention of one-trial inhibitory avoidance training was examined in mice in three separate experiments. In Experiment 1, mice injected with ANI 120 mg/kg and 210 mg/kg exhibited reductions in PS for 9 consecutive hours and ANI 40 mg/kg treated mice for 6 consecutive hours with no PS rebound in all three groups. ANI increased SWS commencing 3 hr postinjection, continuing for 9 consecutive hours and then returning to saline control levels. There were no significant differences between ANI-treated groups in the degree of SWS augmentation. In Experiment 2, Part A, ANI 120 mg/kg and 210 mg/kg but not ANI 40 mg/kg impaired retention measured 72 hr after training. In Experiment 2, Part B, ANI 120 mg/kg and 210 mg/kg induced amnesia from 3 to 9 hr post-training but ANI 40 mg/kg was effective only from 3 to 6 hr. In Experiment 3, the gradient of memory trace susceptibility to disruption by ECS was extended to 3 hr post-training in mice given immediate post-training injections of ANI 40 mg/kg. ANI 20 mg/kg and ANI 10 mg/kg alone or in combination with ECS was ineffective in extending the lability of the memory trace. The results of this study indicate that PS in the 3 hr period after aversively motivated training is not essential for memory processing. We suggest that memory stability and maintenance is dependent on PS occurring over a protracted time period.     

Effects of pre- and post-trial caffeine administrations on simultaneous visual discrimination in three inbred strains of mice

BALB/cJ, DBA/2J, and C57BL/6J mice were injected with caffeine and tested, in the five choice Yerkes-Thompson Bryant-Bovet Nitti apparatus for patterns discrimination, in two sets of experiments. In the first the patterns were opposite oriented oblique bars, in the second U-shaped figures, one opened toward the right, the other toward the left.As concerns the saline injected animals in both sets of experiments, the BALB mice showed the highest learning abilities; in the second set the C57 strain, whose performance had not been different from that of the DBA mice in the first set, performed at the lowest level.Pre- and post-trial caffeine (5 mg/kg) administrations were followed by performance impairment in the BALB strain, while performance improvements were evident in the drugged animals belonging to the other two strains.     

苯环喹溴铵长期经鼻给药对小鼠学习记忆能力的影响

目的观察苯环喹溴铵对小鼠学习记忆能力的影响及其形成原因。方法 50只筛选出的雄性昆明小鼠随机分为5组:溶媒组,苯环喹溴铵高、中、低剂量组(5.86、2.93、1.47mg·kg~(-1))及戊乙奎醚组(2.25mg·kg~(-1)),给药容量为5μL·10g~(-1),经鼻给药,每日1次,持续1mo。以Morris水迷宫和跳台实验测试苯环喹溴铵对其学习记忆能力的影响。另取50只昆明小鼠(雌雄各半)随机分为5组,以LC-ESIMS法测定小鼠在经鼻给予苯环喹溴铵5.86mg·k~g(-1)后10、45min及3、12、48h脑组织和血浆中苯环喹溴铵的浓度(给药后每个时间点各10只小鼠)。结果苯环喹溴铵各剂量组,对小鼠在Morris水迷宫和跳台实验中的学习记忆能力均无明显影响(P>0.05);小鼠在给药后各时间点,脑组织中苯环喹溴铵的浓度均在定量下限以下(苯环喹溴铵在脑匀浆中的定量下限为0.5405μg·L~(-1)),而给药后48h血浆中苯环喹溴铵的浓度为(4.01±0.52)μg·L~(-1)。结论苯环喹溴铵长期经鼻给药对小鼠的学习记忆能力没有影响,可能是由于其难以通过血脑屏障所致。     

脑清宁颗粒剂对小鼠学习记忆能力的影响

目的观察脑清宁颗粒剂对小鼠学习记忆能力的影响.方法以东莨菪碱、亚硝酸钠和乙醇分别造成小鼠记忆获得障碍、记忆巩固障碍和记忆再现障碍,采用Y型迷路法测定小鼠学习记忆能力.结果在3种记忆障碍模型中,预先灌胃给予脑清宁颗粒剂5、10、20 g·kg-1,1次·d-1,连续7 d,可明显提高小鼠的学习记忆成绩(P＜0.001).结论脑清宁颗粒剂对小鼠学习记忆障碍有改善作用.     

雌激素改善小鼠学习记忆的实验研究

目的 :研究雌激素去除 (OVX)与雌激素替代 (ERT)对小鼠T迷宫学习记忆的影响。方法 :3mo鼠龄的雄性C 5 7BL/ 6J小鼠 6 0只 ,随机分 2组 ,分别为假手术组和卵巢切除组 ,每组又分为不给雌激素、给雌激素 7d、给雌激素 4 0d的 3个亚组 ,每组 10只。小鼠摘除卵巢后饲养至 7mo鼠龄进行迷宫实验 ,将 2组小鼠于迷宫测试前 7d和 4 0d分别埋植控释雌激素 (17β 雌二醇 )药丸每丸 0 .18mg ,测试各组小鼠对T迷宫的正确选择次数。结果 :卵巢切除组不给雌激素亚组其正确选择次数明显下降 ,与假手术组的不给雌激素亚组比较 ,d 1,d2和d 3为 (42± 10 ) %vs (5 4± 9) % ,(47± 11) %vs (6 2± 10 ) %和 (5 0± 10 ) %vs (6 8± 10 ) %均P<0 .0 1;给雌激素 7d和 4 0d亚组其正确选择次数明显提高d 1,d 2和d 3为 (5 7± 7) %vs (42±10 ) % ,(6 5± 11) %vs (47± 11) %和 (77± 11) %vs(5 0± 10 ) % (P <0 .0 1) ,而且长期给雌激素亚组其正确选择次数明显高于短期给雌激素亚组。假手术组的不给雌激素和给雌激素组其正确次数差异无显著意义 (P >0 .0 5 )。结论 :雌激素去除明显损害了小鼠的学习记忆能力 ,而雌激素替代可以改善小鼠的学习记忆能力 ,正常小鼠予雌激素负荷并不能影响其学习记忆过程     

远志提取物对小鼠学习记忆的影响

目的:研究远志提取物(Ept-Ⅵ)对小鼠学习记忆功能的影响。方法:利用动物学习记忆计算机在线检测系统,采用东莨菪碱、亚硝酸钠、最大电休克和自然衰老所致小鼠学习记忆障碍模型,通过跳台试验和水迷宫实验对Ept-Ⅵ的益智作用进行了观察。结果:在跳台实验中,连续灌胃给予Ept-Ⅵ30～120 mg·kg-1·d-1,1周可明显改善12月龄BALB／C小鼠的学习和认知能力,使其在获得、巩固、再现阶段停留在安全区时间延长,错误区时间减少;连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1,2周对3 mg·kg-1·d-1东莨菪碱所致小鼠学习记忆障碍有明显的改善作用,表现为小鼠在学习巩固阶段安全区时间延长,错误区时间减少;而连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1, 2周可显著改善最大电休克(MES)所致小鼠学习记忆障碍。在水迷宫实验中,连续灌胃给予Ept-Ⅵ60～240 mg·kg-1·d-1,12周可以缩短亚硝酸钠所致学习记忆障碍小鼠到达水迷宫安全平台／出口的时间。结论:远志提取物能够在学习的多个阶段改善学习记忆障碍模型小鼠的学习记忆功能。     

知母皂苷对学习记忆障碍模型小鼠的作用

目的　研究知母皂苷对化学药物导致小鼠学习记忆能力下降的对抗作用,探讨知母皂苷的促智作用及其机制。方法　以化学药物导致学习记忆障碍模型小鼠为实验对象,以其学习记忆能力为指标,全面考察知母皂苷的促智作用。结果　知母皂苷(10 0、2 0 0、4 0 0mg·kg-1,ip)能对抗记忆障碍模型小鼠学习记忆能力的下降。结论　知母皂苷能有效地促进记忆障碍模型小鼠的学习记忆能力。     

Effects of puromycin on memory for shuttle box extinction in goldfish and barpress extinction in rats

Five experiments were conducted to investigated the generality of puromycin's reported effect on disruption on memory of a recently learned task. The first experiment replicated previous work on acquisition to determine the effectiveness of the procedures used. The second investigated the role of puromycin's low pH in memory disruption. The third experiment used short training and extinction sessions to determine if puromycin retarded retention of extinction. The fourth experiment used longer training and extinction sessions and multiple and delayed injections of puromycin, and the fifth experiment attempted to extend puromycin's effect on avoidance extinction to extinction produced in an appetitive operant task. Puromycin disrupted retention of extinction of both shuttle box avoidance in fish and barpressing in rats. The role of puromycin's pH was negligible.     

芹菜甲素对学习记忆障碍模型小鼠的作用

目的采用化学药物导致小鼠学习记忆能力下降的损伤模型,研究芹菜素的促智作用及其机理。方法用东莨菪碱致记忆获得障碍、亚硝酸钠和电休克致记忆巩固障碍、30%乙醇致记忆再现障碍三种模型小鼠为实验对象,以其学习记忆能力为指标,考察芹菜素的促智作用。结果芹菜素(10、20、40mg.kg-1,i.g),能明显对抗记忆获得、巩固和再现障碍模型小鼠学习记忆能力的下降。结论芹菜素能有效地促进记忆障碍模型小鼠的学习记忆能力。     

胍基琥珀酸促进小鼠学习和记忆的作用(英文)

采用水迷宫实验和一次性被动回避实验 (跳台法和避暗法 ) ,研究了胍基琥珀酸 ( 14,2 8和 56mg·kg- 1,ip)对小鼠学习和记忆的影响 .在水迷宫实验中 ,给小鼠ip胍基琥珀酸 56mg·kg- 1,每日 1次 ,连给 4d ,明显改善小鼠的记忆功能 .无论 1次或连续 4dip上述 3个剂量的胍基琥珀酸对正常小鼠一次性被动回避实验均无明显影响 ,但能明显对抗樟柳碱 ( 5mg·kg- 1,ip) ,亚硝酸钠 ( 12 5mg·kg- 1,sc)和 10 %乙醇 ( 10mL·kg- 1,po)所引起的记忆障碍 .胍基琥珀酸的上述作用近似谷氨酸 ( 30 0mg·kg- 1,ip) .结果表明 ,胍基琥珀酸类似谷氨酸和其他兴奋性氨基酸 ,在调节学习和记忆过程中可能起一定的作用     

Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory

Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.     

多肽P165对糖尿病小鼠学习记忆功能及海马神经元蛋白表达的影响

目的研究多肽P165对糖尿病模型小鼠学习记忆能力及海马神经元蛋白表达的影响。方法用链脲佐菌素诱发小鼠糖尿病模型,应用P165(0.07,0.17,0.3mg·kg-1)灌胃治疗,5wk后进行Morris水迷宫试验;小鼠脑组织海马做Akt、PI3K、P-CREB、Bcl-2、Bax、CytoC免疫组织化学染色;另一部分鼠脑海马,做Bcl-2、Bax抗体蛋白免疫印记。结果①水迷宫试验:糖尿病模型小鼠到达站台游动时间比正常对照组延长(P<0.01);而P165(0.07,0.17,0.3mg·kg-1)灌胃治疗组较DM组动物分别缩短(P<0.01)。②神经免疫组织化学实验及Westernblot结果:糖尿病给予P165小鼠与对照组小鼠海马组织内神经元表达细胞存活相关蛋白及抗凋亡相关蛋白PI3K、Akt、P-CREB、Bcl-2阳性细胞数相似,明显高于糖尿病小鼠(P<0.01);糖尿病给予P165小鼠与对照组小鼠表达凋亡蛋白Bax、CytoC阳性细胞数相似,明显少于糖尿病小鼠(P<0.05)。Westernblot结果相同。结论糖尿病小鼠海马神经元表达细胞存活相关蛋白下降,神经元表达细胞凋亡相关蛋白增加,导致其学习记忆能力下降。P165应用可以使上述蛋白恢复到接近正常,从而改善糖尿病小鼠学习记忆能力。