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PubMed1992

Effect of CDP-choline on learning and memory processes in rodents.

The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP-choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels.

Animals↗
PubMed1995

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Sleep, memory, and learning in off-pump coronary artery bypass patients.

In this study, I examined sleep, memory, and learning in off-pump coronary artery bypass (OPCAB) patients. Sixty-six men and women aged >or=60 years wore actigraphs to record sleep and completed sleep diaries for two 24-hour periods following OPCAB surgery. Prior to discharge from the hospital, participants completed the Pittsburgh Sleep Quality Index (PSQI) and Rey Auditory Verbal Learning Test. No significant correlations were found between habitual sleep, sleep time, efficiency, number, and duration of awakenings, daytime napping, or memory and learning. Nighttime sleep was short with frequent disturbances, and daytime sleep accounted for half the daily sleep time. Participants scored low in learning and delayed recall. These findings suggest the need to assess sleep and cognition in patients recovering from OPCAB surgery.

Age Factors↗
PubMed1988

Validation of a radial maze test for assessing learning and memory in rats.

Choice behavior of rats in a radially symmetrical 6-arm maze, without food reward, was validated for assessing changes in learning and memory following treatment with 4 psychoactive agents. The test is designed for future use in routine toxicity studies with laboratory rodents. Each radial main arm of the maze leads to a T-shaped choice-point with a blind alley on the left and a long angled alley on the right. Order of choice of the radial main arms served to score within-session working memory, by evaluating relative recency of arm reentries. The choice between blind alley and long-angled alley at the T-intersections provided a measure of between-session reference memory. Maze behavior as an indicator for impairment in learning and memory was validated by testing rats treated with d-amphetamine, chlorpromazine, scopolamine and physostigmine. Based on the above evaluations, working memory was found to be severely impaired by 0.3 and 1.0 mg/kg scopolamine, and reference memory to be improved by 0.02 mg/kg physostigmine and 1.0 mg/kg amphetamine. Locomotor activity, in terms of the total number of arm choices per test session, was altered by all substances as expected from previous reports in the literature. The test appears to be a valid and sensitive method for assessing learning and memory in the rat without the use of food reward, and thus well suited for implementation in routine toxicity studies with rodents.

Animals↗
PubMed2004

Protective effect of tetramethylpyrazine on learning and memory function in D-galactose-lesioned mice.

OBJECTIVE: To explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice. METHODS: C57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg x kg(-1) x d(-1)). Normal saline, TMP, and Huperzine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined. RESULTS: In this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice. CONCLUSION: TMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.

Alzheimer Disease↗
PubMed2003

Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia.

AIM: To investigate the effects of extract from Fructus cannabis (EFC) that can activate calcineurin on learning and memory impairment induced by chemical drugs in mice. METHODS: Bovine brain calcineurin and calmodulin were isolated from frozen tissues. The activity of calcineurin was assayed using p-nitrophenyl phosphate (PNPP) as the substrate. Step-down type passive avoidance test and water maze were used together to determine the effects of EFC on learning and memory dysfunction. RESULTS: EFC activated calcineurin activity at a concentration range of 0.01-100 g/L. The maximal value of EFC on calcineurin activity (35 %+/-5 %) appeared at a concentration of 10 g/L. The chemical drugs such as scopolamine, sodium nitrite, and 45 % ethanol, and sodium pentobarbital induced learning and memory dysfunction. EFC administration (0.2, 0.4, and 0.8 g/kg, igx7 d) prolonged the latency and decreased the number of errors in the step-down test. EFC, given for 7 d, enhanced the spatial resolution of amnesic mice in water maze test. EFC overcome amnesia of three stages of memory process at the dose of 0.2 g/kg. CONCLUSION: EFC with an activation role of calcineurin can improve the impaired learning and memory induced by chemical drugs in mice.

Animals↗
PubMed2002

The role of the laterodorsal nucleus of the thalamus in spatial learning and memory in the rat.

The anterior thalamic nuclei appear to play an important role in learning and memory. Connectionally and structurally, the lateral dorsal nucleus is similar to the anterior nuclei. This study tested the hypothesis that the laterodorsal thalamic nucleus (LD) also contributes to these functions. Adult Sprague-Dawley rats received bilateral ibotenic acid lesions of LD, and 2 weeks later the rats were tested in a repeated acquisition water maze task. The control groups displayed a short final escape latency and showed a preference for the correct quadrant in the probe trial. Rats with a lesion restricted to LD (LDL) were mildly impaired in the task, but rats with lesions that destroyed LD and also significantly (50%) damaged the adjacent anterior thalamic nuclei (LDL+) were severely impaired, displaying no improvement in performing the spatial task. In a second experiment, training in the same paradigm for 2 weeks resulted in improved final performance by LDL and control rats but not by LDL+ rats. These findings support the hypothesis that together with the anterior thalamic nuclei, LD plays a role in spatial learning and memory.

Animals↗
PubMed1991

Solvent-associated olfactory dysfunction: not a predictor of deficits in learning and memory.

OBJECTIVE: The aim of the study was to evaluate associations between olfactory dysfunction and aberrations in learning and memory after chronic occupational exposure to mixed hydrocarbon solvents. METHOD: This was a cross-sectional, epidemiologic study of 187 paint manufacturing workers. The authors administered quantitative tests of olfactory function (the University of Pennsylvania Smell Identification Test) and neurobehavioral function (eight computer- and examiner-administered tests of learning and memory) to workers for whom detailed information was available on lifetime occupational exposure to solvents. RESULTS: Olfactory function test scores were positively correlated with performance on seven of eight of the tests of learning and memory in bivariate analyses. After adjustment for important confounding variables (i.e., age, vocabulary score, and cumulative exposure to hydrocarbon solvents) with multiple linear regression, olfactory function scores predicted performance only on the Wechsler Memory Scale Delayed Logical Memory test. CONCLUSIONS: Overall, the data did not reveal that olfactory dysfunction was correlated with decrements in various memory functions.

Adult↗
PubMed2000

Improvement by low doses of nociceptin on scopolamine-induced impairment of learning and/or memory.

The effects of fmol doses of nociceptin/orphanin FQ on scopolamine-induced impairment of learning and/or memory were examined using spontaneous alternation of Y-maze and step-down type passive avoidance tasks. While fmol doses of nociceptin alone had no effect on spontaneous alternation or passive avoidance behavior in normal mice, administration of nociceptin (10 and/or 100 fmol/mouse) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, significantly improved the scopolamine-induced impairment of spontaneous alternation and passive avoidance behavior. This ameliorating effect was not antagonized by nocistatin (0.5 and 5.0 nmol/mouse, i.c.v.), naloxone benzoylhydrazone (2.3, 11.2, and 56.1 micromol/kg, s.c.) or nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). These results indicated that very low doses of nociceptin ameliorate impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that this peptide has bidirectional modulatory effects on learning and memory; impairment at high doses and amelioration at low doses.

Analgesics, Opioid↗
PubMed2005

Thirty years of olfactory learning and memory research in Drosophila melanogaster.

The last 30 years have witnessed tremendous progress in elucidating the basic mechanisms underlying a simple form of olfactory learning and memory in Drosophila. The application of the mutagenic approach to the study of olfactory learning and memory in Drosophila has yielded insights into the participation of a large number of genes in both the development of critical brain regions as well as in the physiology underlying the acquisition, storage, and retrieval of memory. Newer sophisticated molecular-genetic tools have further allowed for the specification and functional dissection of the neuronal circuitry involved in these processes at a systems level. With these advances in our understanding of the genes, neurons, and circuits involved in learning and memory, the field of Drosophila memory research is nearing a state of integration of the bottom up and top down approaches to understanding this form of behavioral plasticity.

Adaptation, Physiological↗
PubMed2005

Effects of Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development on spatial learning and memory.

The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. Chronic exposure to lead (Pb2+) causes deficits of learning and memory in children and spatial learning deficits in developing rats. Brn-3a is a member of the Pit-Oct-Unc (POU) family of transcription factors that is expressed predominantly in neuronal cells. It exists in two forms, with the long form containing 84 amino acids at the N-terminus that are lacking in the short form. The N-terminal domain unique to the long form induces expression of the Bcl-2 gene and protects neuronal cells against apoptosis whereas the C-terminal POU domain common to both forms is sufficient for activating a number of other neuronally expressed genes and stimulating neuronal process outgrowth. We examined Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development and subsequent effects on spatial learning and memory. Two groups of rats were investigated: a control group and a lead-exposed group (0.2% lead acetate in the drinking water of the dam from gestational day 15 to postnatal day 21). Levels of Brn-3a were measured in rat cortex, hippocampus and cerebellum by immunohistochemistry and in situ hybridization, both protein and mRNA levels were reduced in lead-exposed group (p < 0.05). In Morris water maze, we found spatial learning deficits in rats of lead-exposed group (p < 0.05). These data suggest that the alteration of Brn-3a may play a key role in the mechanisms underlying lead neurotoxicity.

Animals↗
PubMed1999

Impaired learning and memory and altered hippocampal neurodevelopment resulting from interleukin-2 gene deletion.

Interleukin-2 (IL-2), the protypical T cell growth factor and immunoregulatory cytokine produced by lymphocytes, has been implicated as a brain neurotrophic factor and neuromodulator. The consequences of the absence of endogenous IL-2 on brain development and function were unknown. Brain IL-2 receptors are enriched in the hippocampal formation, an area critical for the acquisition and consolidation of spatial learning and memory. Thus, we tested the hypothesis that mice lacking IL-2 would exhibit alterations in hippocampal-dependent learning and neurodevelopment. Compared with C57BL/6-IL-2+/+ wild-type mice, we observed that C57BL/6-IL-2-/- gene knockout mice had markedly impaired spatial learning and memory in the Morris water maze. No significant deficits in parameters of learning and memory performance were found in severe combined immunodeficient (SCID) mice (C57BL/6scid), however, suggesting that the impaired spatial learning and memory exhibited by IL-2 knockout mice is not attributable to generalized immunodeficiency resulting from the absence of endogenous IL-2. Examination of other domains of behavioral performance showed that the IL-2 knockout and wildtype mice did not differ in measures of fearfulness or locomotor activity in an elevated plus maze, or in reflexive startle responses to auditory stimuli--although prepulse inhibition of acoustic startle (PPI) was increased significantly in IL-2 knockout mice. The spatial learning and memory impairment in IL-2 knockout mice was accompanied by reductions in hippocampal infrapyramidal mossy neuronal fiber length, a factor shown previously to correlate positively with spatial learning ability. These findings indicate that, in addition to being a pivotal cytokine in immune regulation, IL-2 may play a role in the development and regulation of brain neurons involved in spatial learning and memory.

Acoustic Stimulation↗
PubMed2002

Genetic approaches to molecular and cellular cognition: a focus on LTP and learning and memory.

Long-term potentiation (LTP) is the predominant experimental model for the synaptic plasticity mechanisms thought to underlie learning and memory. This review is focused on the contributions of genetics to the understanding of the role of LTP in learning and memory. These studies have used a combination of genetics, molecular biology, neurophysiology, and psychology to demonstrate that molecular mechanisms of synaptic plasticity are critical for learning and memory. Because of the large scope of this literature, we focus primarily on genetic studies of hippocampal-dependent learning. Altogether, these findings not only demonstrate a role for plasticity in learning, they also lay down the foundations for the new field of molecular and cellular cognition.

Animals↗
PubMed1988

Effects of prenatal administration of phencyclidine on the learning and memory processes of rat offspring.

The effects of prenatal administration of phencyclidine (PCP) on the learning and memory processes of rat offspring were investigated at doses below the level for producing malformations. The offspring prenatally treated with PCP (10 or 20 mg/kg) on days 7 to 17, as well as on days 7 to 21 of gestation, showed disruption of the acquisition of passive avoidance response and pole-climbing avoidance response at the ages of 4 and 7 weeks, respectively. The brain weight of the offspring prenatally treated with PCP was significantly decreased. These results suggest that prenatal PCP administration impairs learning and memory processes of passive and active avoidance tasks and that more attention should be given to the developmental toxicity of PCP.

Animals↗
PubMed1975

Comparative studies on the effect of lithium and haloperidol on learning and memory.

A comparative study of the effect of lithium and haloperidol on the processes of learning and memory is carried out in experiments for training albino rats in a maze. Haloperidol introduced intraperitoneally 1 h before learning in a dose of 0.2 mg/kg deteriorates the learning and long-term memory, while a dose of 2 mg/kg makes these processes impossible. Introduced immediately after learning, haloperidol shows a tendency towards deterioration in the phase of memory consolidation. When administered 1 h before the long-term memory test, haloperidol inhibits reproduction. Lithium chloride administered in a single dose of 200 or 300 mg/kg before and after learning, has no pronounced effect. A tendency towards impairment of learning and memory is manifested only upon administration of doses of 200 mg/kg for 8 days in succession. The differences in the effects of lithium and haloperidol on learning and memory do not support the assumption that their similar effect on the cAMP system (inhibition of the adenylate cyclase in the brain) is essential for the mechanism of their effect on the central nervous system.

Animals↗
PubMed1987

[Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats].

The effects of Y-8894 on learning and memory were studied using the pole climbing avoidance (PCA) response in intact and experimentally induced amnesic rats. The following results were obtained: A single administration of Y-8894 (2.5 mg/kg, i.p.) to experimentally induced amnesic rats significantly antagonized the decrease in the mean number of PCA responses induced by an electroconvulsive shock (ECS). At a higher dose (10 mg/kg, i.p.), however, this effect was reduced. Repeated administration of Y-8894 (5 mg/kg, i.p.) significantly antagonized the facilitation of the extinction of the PCA response induced by exposure to CO2. Repeated administration of Y-8894 (2.5 mg/kg, i.p.) significantly facilitated the learning of the PCA response in intact rats. At a higher dose (5 mg/kg, i.p.), however, this effect was reduced. A single administration of Y-8894 (5 mg/kg, i.p. and 25 mg/kg, p.o.) significantly delayed the extinction of the PCA response in intact rats. These results suggest that Y-8894 has an ameliorative and facilitative effect on learning and memory in experimentally induced amnesic and intact rats.

Amantadine↗
PubMed2004

Recent origin of a hominoid-specific splice form of neuropsin, a gene involved in learning and memory.

Neuropsin is a secreted-type serine protease involved in learning and memory. The type II splice form of neuropsin is abundantly expressed in the human brain but not in the mouse brain. We sequenced the type II-spliced region of neuropsin gene in humans and representative nonhuman primate species. Our comparative sequence analysis showed that only the hominoid species (humans and apes) have the intact open reading frame of the type II splice form, indicating that the type II neuropsin originated recently in the primate lineage about 18 MYA. Expression analysis using RT-PCR detected abundant expression of the type II form in the frontal lobe of the adult human brain, but no expression was detected in the brains of lesser apes and Old World monkeys, indicating that the type II form of neuropsin only became functional in recent time, and it might contribute to the progressive change of cognitive abilities during primate evolution.

Alternative Splicing↗
PubMed2000

Role of nociceptin systems in learning and memory.

This article summarizes our recent finding that the nociceptin system is involved in the regulation of learning and memory. The nociceptin-knockout mice show greater learning ability in the water maze task, an enhanced latent learning in the water finding task, better memory in the passive avoidance task, and further, larger long-term potentiation in the hippocampal CA1 region than wild-type mice. Nociceptin itself induces an impairment of passive avoidance task in wild-type mice, which is reversed by naloxone benzoylhydrazone (NalBzoH). Thus, the nociceptin system seems to play negative roles in learning and memory, and NalBzoH may act as a potent antagonist for the nociceptin receptor.

Animals↗