Effects of beta-adrenergic antagonist,propranolol on spatial memory and exploratory behavior in mice

The beta-adrenergic system has been suggested to be involved in novelty detection and memory modulation. The present study aimed to investigate the role of beta-adrenergic receptors on novelty-based spatial recognition memory and exploratory behavior in mice using Y-maze test and open-field respectively. Mice were injected with three doses of beta-adrenergic receptor antagonist, propranolol (2, 10 and 20 mg/kg) or saline at three different time points (15 min prior to training, immediately after training and 15 min before test). The results showed that higher doses of propranolol (10 and 20 mg/kg) given before the training trial impaired spatial recognition memory while those injected at other two time points did not. A detailed analysis of exploratory behavior in open-field showed that lower dose (2 mg/kg) of propranolol reduced exploratory behavior of mice. Our findings indicate that higher dose of propranolol can impair acquisition of spatial information in the Y-maze without altering locomotion, suggesting that the beta-adrenergic system may be involved in modulating memory processes at the time of learning.     

Effects of pre-training morphine on spatial memory acquisition and retrieval in mice

The opioid system plays an important role in memory processess. Morphine mimics endogenous opioids by acting on opioid receptor in brain to regulate memory. However, the effects of morphine on spatial memory acquisition are controversial. Also, little evidence has suggested that morphine could affect the retrieval of spatial memory. In the current study, effects of pre-training morphine and naloxone on the acquisition vs. retrieval of spatial reference vs. working memory were examined using discrete water maze tasks in C57BL/6 mice. Pre-training morphine administration (7.5 and 15 mg/kg, i.p.) impaired the acquisition of both spatial reference memory and working memory. Motivation to escape from the water maze was not affected by morphine. Pre-test morphine also inhibited the retrieval of spatial working memory but not reference memory. The effects of morphine on the acquisition and retrieval of spatial working memory were eliminated by naloxone pretreatment (1 mg/kg). These results indicate that morphine could differentially modulate a variety of aspects of spatial memory and these effects are mediated by the mu-opioid receptor.     

Effect of enriched environment during adolescence on spatial learning and memory,and voluntary consumption of morphine in maternally separated rats in adulthood

This study was designed to examine the effect of environmental enrichment (EE) during adolescence on spatial learning and memory and voluntary morphine consumption in maternally separated (MS) male and female rats in adulthood. Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from the dams daily for 180 min during postnatal days 2–14. All pups were weaned on day 21. The pups of both sexes were reared in a standard (SE) or enriched (EE) environment during postnatal days 21–50. Then, adulthood rats were tested for spatial learning and memory (Morris Water Maze), and voluntary consumption of morphine using a two-bottle choice paradigm (TBC). We found that the MS/SE rats showed longer escape latencies to find the platform on the third (the male) and fourth (the female) days of training than No MS/SE rats. Also, exposure to EE shortened the latency to escape in the male and female MS rats as training progressed than MS/SE rats. Moreover, the No MS/EE and MS/EE male rats spent significantly more time in the target zone compared with the SE control groups in the probe test. We also found that voluntary morphine consumption was higher in the male and female MS/SE than No MS/SE rats, while it was lower in the male and female MS/EE rats. The present results have shown that EE treatment may have potential therapeutic application for the prevention of the development of drug addiction and recovery from cognitive deficits following neonatal MS during adulthood.     

Effects of sub-anesthetic doses of ketamine on rats' spatial and non-spatial recognition memory

There are experimental evidences indicating that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hyperactivity, stereotypies and ataxia). The present study was designed to investigate the effects of ketamine on rats' non-spatial and spatial recognition memory. For this purpose the object recognition and the object location task were selected. Pre- or post-training systemic administration of ketamine (0.3, 1 and 3 mg/kg; i.p.) in a dose-dependent manner disrupted animals' performance in both these recognition memory paradigms, suggesting that this compound affected pre- and post-training memory components. The current results indicate that the non-competitive NMDA antagonist ketamine may modulate either spatial or non-spatial recognition memory.     

Ganglioside GQ1b improves spatial learning and memory of rats as measured by the Y-maze and the Morris water maze tests

Gangliosides are major components of cell membranes and are particularly enriched in the mammalian brain where they represent the major lipid constituents of the neuronal cell surface. In the central nervous system, gangliosides have a close connection to many neurophysiological functions related to neurogenesis, proliferation, synaptogenesis, and synaptic transmission. The previously reported effect of the tetra-sialoganglioside GQ1b in hippocampal CA1 neurons of brain slices showed that GQ1b enhanced ATP-induced long-term potentiation (LTP). However, there has been no clear evidence of the effects of GQ1b on learning and memory as measured using behavioral test. In the present study, we performed the Y-maze and the Morris water maze (MWM) tests to reveal the effects of GQ1b on spatial learning and memory following intracerebroventricular (ICV) injection of GQ1b. GQ1b-treated rats showed highly increased performance on the Y-maze and the MWM tests without any significant alteration of basal locomotor activity. Therefore, our behavioral data strongly suggest that GQ1b improves spatial learning and memory in rats. Also, these data support the previous finding that GQ1b treatment in hippocampal CA1 neurons of rodent brain slices increased ATP-induced LTP.     

吗啡成瘾小鼠对正常小鼠学习记忆力能力的影响

目的:用BALB/C小鼠建立动物模型,观察吗啡成瘾戒断小鼠对其周围的正常小鼠学习记忆能力的影响。方法:将吗啡成瘾戒断小鼠与正常小鼠同笼饲养,然后用Morris水迷宫实验测定正常小鼠的学习记忆能力,应用RT-PCR的方法检测正常小鼠海马中PKCa、GABA分子表达的变化。结果:水迷宫实验证明,与生理盐水组相比,实验组小鼠的学习记忆能力明显降低(P<0.05),海马中PKCa和DABA的表达都明显升高(P<0.05)。     

Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice

The retinal degeneration Pde6b^rd1 (rd) mutation can be a major pitfall in behavioral studies using tg2576 mice bred on a B6:SJL genetic background, 1 of the most widely used models of Alzheimer's disease. After a pilot study in wild type mice, performance of 8- and 16-month-old tg2576 mice were assessed in several behavioral tasks with the challenge of selecting 1 or more task(s) showing robust memory deficits on this genetic background. Water maze acquisition was impossible in rd homozygotes, whereas Y-maze alternation, object recognition, and olfactory discrimination were unaffected by both the transgene and the rd mutation. Spatial memory retention of 8- and 16-month-old tg2576 mice, however, was dramatically affected independently of the rd mutation when mice had to recognize a spatial configuration of objects or to perform the Barnes maze. Thus, the latter tasks appear extremely useful to evaluate spatial memory deficits and to test cognitive therapies in tg2576 mice and other mouse models bred on a background susceptible to visual impairment.     

Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase

Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness. Homozygotes evidenced improved performance in spontaneous alternation, an index of immediate spatial working memory; this effect appeared more substantive in males and was reflected in performance in aspects of the Barnes maze, an index of spatial learning/memory. Heterozygotes evidenced impaired performance in object recognition, an index of recognition memory; this effect was evident for both sexes at a retention interval of 5 min but appeared more enduring in males. There were no material effects for either genotype in relation to sociability or social novelty preference. While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. We have reported recently, using similar methods, that mice with deletion of the schizophrenia risk gene neuregulin-1 evidence disruption to social behavior, with little effect on spatial learning/working memory. The data suggest that catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome.     

吗啡依赖对小鼠睾丸组织的影响及其相关机制分析

为了解吗啡依赖对小鼠睾丸发育及其功能的影响 ,研究了吗啡依赖对睾丸生精细胞凋亡的影响及其可能机制。以剂量递增法皮下注射吗啡建立吗啡成瘾小鼠模型 ,用纳洛酮催促戒断 ,观察戒断症状 ,采用原子吸收、放射免疫分析和原位缺口平移 (ISNT)技术观察睾丸细胞锌和钙调素 (CaM)含量、睾丸超氧歧化酶 (SOD)、还原型谷胱甘肽过氧化物酶 (GSH Px)活性和睾丸组织中凋亡细胞数目。结果表明 ,与对照组相比 ,吗啡依赖组和纳洛酮催促戒断组躯体运动神经功能和植物神经功能亢进 ,睾丸锌和CaM含量减少 ,睾丸SOD、GSH Px活性降低 ,睾丸组织中生精细胞凋亡数目明显增多 (P <0 0 5或P <0 0 1)。吗啡依赖小鼠可诱导睾丸组织中细胞凋亡 ,这种变化可能与睾丸组织中锌和CaM含量减少、睾丸SOD和GSH Px活性降低有关。     

Effects of sex and APOE epsilon4 on object recognition and spatial navigation in the elderly

To determine effects of APOE epsilon4 (epsilon4) on cognitive performance of healthy elderly, 116 nondemented elders (mean age 81 years) were cognitive tested. The established tests Faces, Family Pictures, Spatial Span Forward and Backward, and the object recognition and spatial navigation tests developed in our laboratory were used as cognitive tests. Salivary samples were collected to determine APOE genotype and salivary testosterone and cortisol levels. Non-epsilon4- and epsilon4-carrying men and women did not differ in age, Mini-Mental State Examination, Wide Range Achievement Test-Reading, Beck Anxiety Inventory, or reaction time scores. There was an effect of epsilon4 on the object recognition and spatial navigation tests, with non-epsilon4 carriers outperforming epsilon4 carriers, but not in the other cognitive tests. No relationship was found for sex and epsilon4 status or sex and performance during the hidden session of Memory Island. In men, salivary cortisol levels correlated with object recognition. These results show that object recognition and spatial navigation tests are useful to assess cognitive function in the elderly.     

淋巴滞留性脑病模型空间记忆的改变

目的 :探讨大鼠淋巴滞留性脑病时空间记忆的变化。方法 :选用雄性Wistar大鼠 3 2只 ,随机分为模型组、假手术组。训练受试大鼠学会延缓的位置非匹配作业 ,该作业包括信息游泳和选择游泳两部分 ,前者表示空间参考记忆 ,后者表示空间工作记忆。将模型组大鼠颈淋巴干结扎制造淋巴滞留性脑病模型。分别于术后 6～ 8天及 1 5～ 1 7天检测已形成的空间记忆。结果 :术后 6～ 8天模型组大鼠信息游泳的游泳时间较假手术组明显延长 (P <0 .0 1 ) ,但二者选择游泳的正确率及游泳时间均无显著性差异 (P >0 .2 3 ,P >0 .1 9)。结论 :大鼠淋巴滞留性脑病损害空间参考记忆 ,但未影响空间工作记忆     

Object recognition memory and BDNF expression are reduced in young TgCRND8 mice

The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse.     

Young hippocampal neurons are critical for recent and remote spatial memory in adult mice

New granule cells are continuously generated throughout adulthood in the mammalian hippocampus. These newly generated neurons become functionally integrated into existing hippocampal neuronal networks, such as those that support retrieval of remote spatial memory. Here, we sought to examine whether the contribution of newly born neurons depends on the type of learning and memory task in mice. To do so, we reduced neurogenesis with a cytostatic agent and examined whether depletion of young hippocampal neurons affects learning and/or memory in two hippocampal-dependent tasks (spatial navigation in the Morris water maze and object location test) and two hippocampal-independent tasks (cued navigation in the Morris water maze and novel object recognition). Double immunohistofluorescent labeling of the birth dating marker 5-bromo-2'deoxyuridine (BrdU) together with NeuN, a neuron specific marker, was employed to quantify reduction of hippocampal neurogenesis. We found that depletion of young adult-generated neurons alters recent and remote memory in spatial tasks but spares non-spatial tasks. Our findings provide additional evidence that generation of new cells in the adult brain is crucial for hippocampal-dependent cognitive functions.     

Long-term object location memory in rats: Effects of sample phase and delay length in spontaneous place recognition test

This study investigates the effects of sample phase and delay length on discrimination performance in the spontaneous place recognition (SPR) test in rats. Rats were allowed to explore an arena where two identical objects were presented for 5–20 min (sample phase). After a delay interval, rats were placed again in the same arena but one of the two objects was moved to a novel place (test phase). Results showed that when the sample phase was as long as 20 min, rats preferentially explored the moved object during the test phase even after a 6–24 h delay was interposed. Further sequential and cumulative analyses of the test phase revealed that the preference for the object in a novel place was evident in the first and 2nd min of the test phase in rats with a longer sample phase duration. Correlation analysis showed that locomotor activity and object exploration in the sample phase were not decisive factors in spatial memory performance. The present results demonstrate the importance of the sample phase exposure time and the test phase length.     

Dipeptide preparation Noopept prevents scopolamine-induced deficit of spatial memory in BALB/c mice

The effect of original nootropic preparation Noopept on learning and long-term memory was studied with BALB/c mice. Scopolamine (1 mg/kg) impaired long-term memory trace, while Noopept (0.5 mg/kg) had no significant effect. Noopept completely prevented the development of cognitive disorders induced by scopolamine (blockade of muscarinic cholinergic receptors). Our results confirmed the presence of choline-positive effect in dipeptide piracetam analogue Noopept on retrieval of learned skill of finding a submerged platform (spatial memory). We conclude that the effectiveness of this drug should be evaluated in patients with Alzheimer’s disease. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 407–410, April, 2007     

Effects of ectopias and their cortical location on several measures of learning in BXSB mice

About half of BXSB/MpJ‐ Yaa mice have ectopias, which are misplaced clusters of neurons located in layer I of cortex. This study replicated several previous findings showing that there are learning differences between mice with ectopias and those without. In addition, we had sufficient numbers of ectopic mice to investigate if ectopics learned differently depending on the cortical location of the ectopia(s). Mice with at least one ectopia located in prefrontal cortex were initially impaired in learning the Morris maze, as well as relearning the Lashley maze when it was inverted, but learned better in the radial‐arm maze when compared to ectopic mice with ectopias located in nonprefrontal regions of cortex. Mice with at least one ectopia in motor cortex learned the Lashley maze better than mice with ectopias located outside motor cortex. In sum, the cortical location of the ectopia(s) affected learning performance in certain tasks within the ectopic group, but regardless of the cortical location of the ectopia(s), ectopics still learned differently than nonectopics in several tasks. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 286–300, 2001     

Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGluR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGluR5 activation in some types of hippocampus-dependent spatial learning.     

硫胺素缺乏对小鼠学习记忆能力的影响

为研究硫胺素缺乏对小鼠学习记忆能力的影响，我们随机地将４０只昆明雄性小鼠分成对照、对饲和硫胺素缺乏组。经２４天饲养后，硫胺素缺乏组小鼠毛发稀疏、体重显著性地低于对照和对饲组，ＴＰＤ效应值显著地高于对照和对饲组。硫胺素缺乏组小鼠完成水迷宫所需要的时间和平均错误次数均显著性地高于对照和对饲组。在一次性回避反应的跳台和避暗测验中，硫胺素缺乏组小鼠避暗反应的平均潜伏期显著显著性地短于对照组，且平均错误次数     

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.     

Reduced nocturnal morphine analgesia in mice following a geomagnetic disturbance

Latency to respond to an aversive thermal stimulus and the degree of analgesia induced by morphine were examined in mice injected with either isotonic saline or morphine sulfate (10 mg/kg) during midscotophase of a 12:12 h LD cycle. When mean response latencies were compared to the degree of geomagnetic disturbance (Ap index) present on test days, it was found that during the geomagnetic storm on December 17th, 1982, a significant reduction (P<0.01) in response latency was evident in both saline- and morphine-treated mice. The reduction in response latencies was greater, and lasted longer in the morphine-treated animals. It is suggested that the pineal gland may mediate this biomagnetic effect.