青、老年大鼠在Morris水迷宫中的学习记忆行为

本实验观察了22～24月龄老年大鼠和5～6月龄青年大鼠在Morris水迷宫中的学习记忆行为,并用定量分析方法比较两组动物在定位航行及空间搜索试验中的学习记忆,结果表明老年大鼠的寻找平台潜伏期明显延长,而其跨平台次数及在平台象限的游泳路线长度并未减少.提示24月龄老年大鼠获取学习记忆的能力受损伤而保持记忆的能力维持正常,这可能与二种功能衰老的不同速度及不同神经基础有关.     

吗啡成瘾对大鼠及小鼠学习与记忆能力影响的实验研究

目的 研究吗啡成瘾对大鼠及小鼠学习与记忆能力的影响。方法 将２４只ＳＤ大鼠昆明小鼠分别随机分成３组;即吗啡成瘾组、吗啡成瘾后戒断组和对照组。然后分组对动物进行Ｍorris水迷宫训练。结果（1）在Morris水迷宫掩蔽平台次训练中,吗啡成瘾组动物（大鼠和小鼠）的逃避潜伏期对与对照组及吗啡戒断组动物相比,均明显延长（P＜0．01）;（2）对照组动物的逃避潜伏期最短;（3）在Morris水迷宫可见平台学习中,无论是大鼠还是小鼠,三组动物逃避潜伏期均随着学习训练逐渐缩短,无明显组间差别（P＞0．05）。结论 吗啡成瘾可明显损害动物的学习记忆能力。     

电针肾俞、膈俞、百会穴对拟血管性痴呆学习记忆障碍小鼠水迷宫实验的影响

目的　观察电针肾俞、膈俞、百会穴对拟血管性痴呆小鼠学习记忆障碍的影响。方法　复制脑缺血再灌注拟血管性痴呆小鼠模型 ,并电针肾俞、膈俞、百会穴 ,分别于术后 7天、15天、30天 ,与药物喜德镇对照 ,采用水迷宫法 ,记录游全程时间、错误次数。结果　造模导致了小鼠学习与记忆能力下降 ,表现为游全程时间延长 ,错误次数增加 ,且随着观察时间的延长 ,这种改变逐渐加重。电针和喜德镇均可使模型小鼠的游全程时间缩短 ,错误次数减少 ,但电针组于 7天和 30天时 ,成绩显著优于药物组。结论　电针肾俞、膈俞、百会穴对模型小鼠学习与记忆能力下降有改善和提高作用     

Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats

The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of ⁹-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED₅₀=0.13 mg/kg). ⁹-THC and WIN-55,212-2 disrupted mazechoice accuracy at equipotent doses (ED₅₀ values =2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of ⁹-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED₅₀=8 µg/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.     

Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat

The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drug effects (Jones and Cole 1995). The drugs tested were FG 7142 (0–100 mg/kg),-CCE (0–30 mg/kg), ZK 132 556 (0–100 mg/kg), ZK 90 886 (0–30 mg/kg) and Ro 15–4513 (0–30 mg/kg). In addition, to allow a comparison with previous studies, the effects of three reference substances, DMCM (0–2.5 mg/kg), pentylenetetrazol (PTZ; 0–30 mg/kg) and yohimbine (0–5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15–4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%. In contrast, the other BZR partial inverse agonists, ZK 132 553 and ZK 90 886, did not significantly reduce the duration of open arm exploration, even at doses that produced greater than 95% receptor occupancies.-CCE also did not reduce open arm exploration at any dose tested (0–30 mg/kg). The GABA shift, a biochemical index of intrinsic activity, indicates that these latter three compounds are more inverse agonistic than Ro 15–4513. In summary, these results demonstrate that not all BZR receptor partial inverse agonists have anxiogenic-like activity in the rat plus maze, and that the GABA shift, a biochemical index of intrinsic efficacy, does not predict which BZR partial inverse agonists are anxiogenic.     

Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats

The brain derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trials. In the present study the effects of early postnatal administration of Cerebrolysin (Cere, 10 mg/ml peptides) or an enriched peptide fraction of Cere (E021, 80.6 mg/ml peptides) were investigated in young, young adult, and old adult rats. Rat pups received the drugs or saline for control on postnatal days 1–7. The animals were tested in the Morris water maze (MWM) either in the 5th week, in the 3rd or the 16th month of life for 6 consecutive days (test days 1–6), eight trials per day. In order to prevent the chance finding of the hidden platform, the rigid underwater platform was replaced by a collapsible island, resting at the bottom of the pool. The platform was raised when the animal stayed in the target area for 2 s. In the young and young adult rats both Cere and E021 treated rats showed shorter escape latencies than saline treated controls on all 6 test days. No significant differences in the swimming speed were evaluated for the young rats, although in 3-month-old drug-tested animals a moderate increase of the swimming speed was investigated. For 16-month-old animals no significant differences in either escape latencies or swimming speed was found. Summarizing, early postnatal application of Cere or E021 improved the spatial learning and memory of young rats and led to long-lasting behavioural effects at least up to 3 months after treatment.     

不同发育期铅暴露对大鼠空间认知能力的影响

用不同发育期大鼠的接铅史来探讨铅暴露的敏感期及铅对年轻大鼠空间认知能力的影响。结果发现,生前和生后持续接铅的染毒１组和经母体间接接铅的染毒３组,两者Ｍｏｒｉｓ水迷宫的测试成绩均显著低于对照组,而断乳后接铅的染毒２组,虽然血铅水平显著增高,但脑铅水平和水迷宫测试成绩却与对照组无差别,提示在神经发育早期（胎儿期和婴儿期）对铅更敏感。     

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization

This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.     

Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.

Soman, a powerful inhibitor of acetylcholinesterase, causes an array of toxic effects in the central nervous system including convulsions, learning and memory impairments, and, ultimately, death. We report on the protection afforded by postexposure antidotal treatments, combined with pyridostigmine (0.1 mg/kg) pretreatment, against these consequences associated with soman poisoning. Scopolamine (0.1 mg/kg) or caramiphen (10 mg/kg) were administered 5 min after soman (1.2 LD50), whereas TAB (i.e., TMB4, atropine, and benactyzine, 7.5, 3, and 1 mg/kg, respectively) was injected in rats concomitant with the development of toxic signs. Atropine (4 mg/kg) was given to the two former groups at the onset of toxic symptoms. Caramiphen and TAB completely abolished electrographic seizure activity while scopolamine treatment exhibited only partial protection. Additionally, no significant alteration in the density of peripheral benzodiazepine receptors was noted following caramiphen or TAB administration, while scopolamine application resulted in a complex outcome: a portion of the animals demonstrated no change in the number of these sites whereas the others exhibited markedly higher densities. Cognitive functions (i.e., learning and memory processes) evaluated using the Morris water maze improved considerably by the three treatments when compared to soman-injected animals; the following rank order was observed: caramiphen > TAB > scopolamine. Additionally, statistically significant correlations (r = 0.72, r = 0.73) were demonstrated between two learning parameters and [3H]Ro5-4864 binding to brain membrane. These results show that drugs with a pharmacological profile consisting of anticholinergic and antiglutamatergic properties such as caramiphen and TAB, have a substantial potential as postexposure therapies against intoxication by organophosphates.     

Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by α-fluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H_1-antagonist pyrilamine (1 μg/site, ih), but not by H_2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits,