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At least 703 records · Page 39Linked to original sources
PubMed1999

Administration of prosaposin ameliorates spatial learning disturbance and reduces cavity formation following stab wounds in rat brain.

The effectiveness of prosaposin as a neurotrophic factor was investigated using rats with bilateral stab wounds, injecting 240 ng per day of prosaposin for 3 days. In Morris water maze task, after 3 weeks postoperation, the stab-wounds rats show significant impairment in acquisition compared with the sham-operated rats. In the transfer test the mean number of crossings of the platform place in stab-wounds was significantly lower than that in sham-operated rats (P < 0.01). The stab-wounds rats treated with prosaposin showed significant improvement (P < 0.05). The cavities following stab wounds in the rats treated with prosaposin were significantly smaller than those in the rats treated with (P < 0.05). Our data support that prosaposin is likely to be a new agent for brain injury.

Animals↗
PubMed1999

The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism.

We have previously reported that rapid eye movement sleep deprivation (REMSD), induced by the flower pot technique, causes a deficit in reference spatial memory and increases rates of serotonin (5-HT) metabolism in the brain. In this study we used increased concentrations of dietary valine to inhibit tryptophan (TRP) transport across the blood-brain barrier in an attempt to modify the REMSD-induced increase of 5-HT metabolism. Rats were fed either a control diet or the same diet supplemented to 2% by weight valine, and were allocated to one of three experimental groups: cage control (CC), stress tank control (TC), or REMSD. Reference and working spatial memory of all rats was tested in a Morris water maze on Days 2, 3, and 4. REMSD produced a significant decrement in reference memory on Days 2 and 4, independent of dietary condition. The valine diet had a detrimental effect on the reference memory of TC rats on Day 2 but not Day 4. Measurements made on Day 4 indicated that the valine diet decreased brain TRP only in the CC rats. In contrast, the valine diet did not prevent increases in brain TRP or 5-HT metabolism in REMSD rats, and increased hypothalamic and brain stem TRP concentrations and the hippocampal 5-HIAA/5-HT ratio in TC rats. These results indicate that dietary valine does not prevent REMSD-induced changes in spatial memory or serotonin metabolism, although it does reduce brain TRP in nonstressed rats.

Animals↗
PubMed2001

Pharmacological enhancement of synaptic efficacy, spatial learning, and memory through carbonic anhydrase activation in rats.

CA1 pyramidal cells were recorded in rat hippocampal slices. In the presence of carbonic anhydrase activators, comicrostimulation of cholinergic inputs from stratum oriens and gamma-aminobutyric acid (GABA)ergic inputs from stratum pyramidale at low intensities switched the hyperpolarizing GABA-mediated inhibitory postsynaptic potentials to depolarizing responses. In the absence of the activators, however, the same stimuli were insufficient to trigger the synaptic switch. This synaptic switch changed the function of the GABAergic synapses from excitation filter to amplifier and was prevented by carbonic anhydrase inhibitors, indicating a dependence on HCO. Intralateral ventricular administration of these same carbonic anhydrase activators caused the rats to exhibit superior learning of the Morris water maze task, suggesting that the GABAergic synaptic switch is critical for gating the synaptic plasticity that underlies spatial memory formation. Increased carbonic anhydrase activity might, therefore, also enhance perception, processing, and storing of temporally associated relevant signals and represents an important therapeutic target in learning and memory pharmacology.

Acetazolamide↗
PubMed2001

The conjoint importance of the hippocampus and anterior thalamic nuclei for allocentric spatial learning: evidence from a disconnection study in the rat.

A disconnection procedure was used to test whether the hippocampus and anterior thalamic nuclei form functional components of the same spatial memory system. Unilateral excitotoxic lesions were placed in the anterior thalamic (AT) nuclei and hippocampus (HPC) in either the same (AT-HPC Ipsi group) or contralateral (AT-HPC Contra group) hemispheres of rats. The behavioral effects of these combined lesions were compared in several spatial memory tasks sensitive to bilateral hippocampal lesions. In all of the tasks tested, T-maze alternation, radial arm maze, and Morris water maze, those animals with lesions placed in the contralateral hemispheres were more impaired than those animals with lesions in the same hemisphere. These results provide direct support for the notion that the performance of tasks that require spatial memory rely on the operation of the anterior thalamus and hippocampus within an integrated neural network.

Animals↗
PubMed1998

Stimulation of 5-HT1A receptors in the dorsal raphe reverses the impairment of spatial learning caused by intrahippocampal scopolamine in rats.

This study investigated the effect of stimulating 5-HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 microg/microL scopolamine injected in the CA1 region of the dorsal hippocampus in rats performing a two-platform spatial discrimination task. At 1 (but not 0.2) microg/0.5 microL administered in the dorsal raphe on each acquisition training day 5 min before bilateral intrahippocampal injection of 4 microg/microL scopolamine, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairment of choice accuracy by intrahippocampal scopolamine. Administered into the dorsal raphe at 0.2 and 1 microg/0.5 microL, WAY 100635, a 5-HT1A receptor antagonist, had no effect on rats' performance or on the impairment caused by intrahippocampal scopolamine but dose-dependently antagonized the effect of 1 microg/0.5 microL 8-OH-DPAT on the scopolamine-induced deficit. The results show that stimulation of presynaptic 5-HT1A receptors in the dorsal raphe reverses the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. Together with a previous study showing that blockade of postsynaptic hippocampal 5-HT1A receptors antagonized the effect of intrahippocampal scopolamine in the two-platform spatial discrimination task (Carli et al., 1995b), the results suggest that drugs with presynaptic stimulatory and postsynaptic blocking actions on 5-HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol.

Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities.

Animals↗
PubMed1989

The effects of undernutrition during early life on spatial learning.

Recent research has shown that a lengthy period of undernutrition during early postnatal life can cause alterations in the morphological structure of the dentate gyrus. As this region is involved in the control of spatial memory, we decided to investigate whether undernourished rats also showed any deficits in this aspect of behaviour. Rats were undernourished from about birth until either 30 or 60 days of age and then nutritionally rehabilitated for a lengthy period before testing. There were significant differences in the body weight of control and undernourished rats in each experiment. The testing procedure involved rats being placed in a large pool of opaque water. They were required to swim to find a hidden platform located just below the water surface onto which they could escape. Each rat had to perform this test 20 times over a period of 3 days. The time taken and the total distance swum by each rat during each trial was measured. In Experiment 1, rats were familiarised with the water before testing took place, whereas in Experiment 2 they were not. There were no significant differences in the latency to find the platform or the distance swum between well-fed control and previously undernourished rats in either experiment. In conclusion, in our experiments we could not demonstrate that undernutrition during early life caused any deficits in spatial memory performance.

Animals↗
PubMed1998

Assessing cognitive functions in tree shrews: visuo-spatial and spatial learning in the home cage.

We developed a holeboard paradigm to investigate the cognitive abilities of tree shrews (Tupaia belangeri). The design allows animals to be tested in their homecages, which reduces possible confounding and stress factors, such as transfer to a special testing arena, food deprivation or other restraints. Nine male tree shrews performed four visuo-spatial and one spatial trial per day in two blocks of 5 consecutive days. Tree shrews needed only 1 day, that is five trials, to learn the complex holeboard paradigm. From the second day onwards the learning scores remained almost stable. To demonstrate the applicability of this paradigm in studies on the influence of stress on cognitive functions, three animals were subjected to and tested under psychosocial stress conditions on 2 consecutive days. Since the experimental animals also performed the task under stressful conditions the home cage holeboard paradigm is a valid tool to study the development of stress induced cognitive impairments.

Animals↗
PubMed1995

Phencyclidine injections into the dorsal hippocampus disrupt long- but not short-term memory within a spatial learning task.

Since the hippocampus is likely to be a major site of phencyclidine (PCP) action, the effects of various doses of PCP (1.8, 18 or 36 nM) as well as 3.6 nM MK-801 or saline injected directly into the dentate gyrus of the hippocampus was tested for acquisition of a spatial navigation task (dry land version of a water maze) using a paradigm that assesses short term memory based on learning within a day and long term memory based on learning between days. Results indicated that relative to saline or 1.8 nM PCP injected rats, rats with 18 or 36 nM PCP or 3.6 nM MK-801 injections were impaired in acquisition of the task as measured by increased distances traveled to find the food location between days but not within days. In additional experiments 36 nM PCP or 3.6 nM MK-801 did not produce any deficits in the acquisition of an object discrimination task. It is suggested that PCP through its blocking action of the NMDA receptor in the dentate gyrus or CA1 region of the dorsal hippocampus mediates the consolidation of new spatial location information.

Animals↗
PubMed1982

Cortical noradrenaline depletion eliminates sparing of spatial learning after neonatal frontal cortex damage in the rat.

The possibility that cortical noradrenaline (NA) is necessary for the sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage sustained neonatally was better than by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical noradrenaline by means of neonatal 6-hydroxydopamine (6-OHDA) administration. NA depletion alone did not affect spatial localization. These data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex.

Animals↗
PubMed2006

Mild forced treadmill exercise enhances spatial learning in the aged rat.

This study addresses whether or not mild, forced treadmill exercise improves learning and increases neurotrophin levels in the basal forebrain (BF). Neurotrophin deficits in the BF have been implicated in Alzheimer's disease, and physical exercise increases neurotrophins. Aged rats exercised for 7 weeks found the hidden platform faster than controls (F(1, 10)=14.6, p<0.05), and swam shorter pathlengths (F(1, 10)=12.6, p<0.05), with no difference in swim speed. Neurotrophins did not differ.

Aging↗
PubMed2005

Spatial learning deficits and emotional impairments in pentylenetetrazole-kindled rats.

Pentylenetetrazole (PTZ) is a chemical kindling agent used to examine the efficacy of potential anticonvulsants in rats. However, the extent to which PTZ mimics postseizure symptoms of epilepsy has not been thoroughly examined. This study assessed whether PTZ-induced seizures produce cognitive and emotional deficits that mimic those observed in many epileptic patients. Rats were given 30mg/kg PTZ or vehicle (intraperitoneally) every other day for 28 days. Those rats exhibiting consistent seizure activity were tested for learning ability and emotional reactivity, beginning 1 week following a single challenge dose of PTZ. Rats given PTZ made more reference memory errors in a radial arm water maze task, and exhibited emotional abnormalities in the forced swim test, the systematic handling test, and the open-field exploratory maze. Histological analysis revealed neuronal loss in the CA1 area and increased mossy fiber sprouting in the dentate gyrus, similar to what is observed in human epilepsy. These results indicate that PTZ kindling provides a useful model of postseizure dysfunction, which can serve as a screen for potential treatments for those cognitive, emotional, and neuropathological deficits that resemble those symptoms observed in human epilepsy.

Affective Symptoms↗
PubMed2006

Potentiation, overshadowing, and blocking of spatial learning based on the shape of the environment.

Rats were trained in Experiment 1 to find a submerged platform in 1 corner of either a rectangular or a kite-shaped pool. When the walls creating this corner were a different color than the opposite walls, then learning about the shape of the pool was potentiated in the kite but not in the rectangle. Experiments 2-4 revealed that learning about the rectangle can be overshadowed and blocked when information about the wall color indicates the location of the platform. The results mimic findings that have been obtained with Pavlovian conditioning, and they challenge the claim that learning about the shape of the environment takes places in a dedicated geometric module.

Animals↗
PubMed1994

Protein kinase C activity in the hippocampus following spatial learning tasks in mice.

Protein kinase C (PKC) is highly concentrated in the hippocampus and is thus a possible neural substrate of learning and memory. This study was designed to determine whether partial acquisition (i.e., the minimal amount of training leading to above-chance performance) of a spatial discrimination in an eight-arm radial maze alters hippocampal PKC activity. Mice were sacrificed at different times (5 minutes, 1 hour, 24 hours) after the second learning session, and PKC activity was measured in both cytosolic and membrane fractions of the hippocampus. In order to determine which component of the task was involved in the alterations in enzymatic activity, hippocampal PKC activity was also measured in a group of mice that was allowed to explore the maze freely. Significantly less PKC activity was found in the cytosolic fraction from the trained animals than from the quiet or active control groups. No differences were observed between the quiet and active controls. In contrast, there were no significant between-groups differences in membrane-bound PKC activity, although a negative correlation between the membrane-bound PKC activity and learning scores (accuracy) was noted. These results suggest that hippocampal PKC activity is involved essentially in the associative component of the task. The lack of learning-induced alterations in membrane-bound PKC activity and the negative correlation between this enzymatic activity and learning accuracy are discussed.

Animals↗
PubMed1993

Enhanced disruptive spatial learning effect after sufentanil in renal hypertensive rats versus normotensive rats.

The effects of the peripherally administered sufentanil citrate (S), a potent opioid agonist with high affinity for mu receptors on the spatial navigation task, were tested in normotensive Wistar (NR) and renal hypertensive rats (RHR). Rats were injected subcutaneously once daily in doses of 0.25 or 1 microgram/kg S before the water maze training. In NR rats, weak effects of 0.25 micrograms/kg S and impairments after 1 microgram/kg S were seen, whereas in RHR 0.25 and 1 microgram/kg S showed clearcut impairments. These data from the Morris water maze task support previous reports that RHR have an increased sensitivity for opioid agonists.

Animals↗
PubMed1993

Hippocampal synaptic enhancement and spatial learning in the Morris swim task.

The authors attempted to replicate the study of Castro, Silbert, McNaughton, and Barnes (1989) in which it was concluded that bilateral saturation of hippocampal synaptic enhancement produced a deficit in acquisition of a spatial navigation problem in the Morris swim task. The original protocol was followed as closely as possible, but no effect of long-term enhancement (LTE) saturation on spatial performance in this task was found. This negative result suggests either that the previous finding using the swim task reflected statistical error or that some as yet undetermined variable is of critical importance in this phenomenon. The present negative finding also raises a question concerning the reproducibility of the earlier results of McNaughton, Barnes, Rao, Baldwin, and Rasmussen (1986) in which LTE saturation apparently led to a prolonged deficit on a different spatial task. Although negative results in such experiments do not constitute grounds for rejecting the underlying hypothesis, the present lack of a positive effect renders uncertain, for the time being, one of the lines of experimental support for the theory that LTE at hippocampal synapses reflects a mechanism for the associative, distributed storage of new spatial information.

Animals↗
PubMed1992

D-cycloserine reverses the working memory impairment of hippocampal-lesioned rats in a spatial learning task.

It is shown that D-cycloserine has cognition-enhancing properties in quinolinic acid hippocampal-lesioned rats. Lesioned rats had a severe impairment of working memory in an allocentric spatial reversal paradigm in the 8-arm maze, and performance could be restored with 12 mg/kg i.p. D-cycloserine, given 30 min before testing. The present findings favour the testing of D-cycloserine for clinical efficacy in patients with Alzheimer's disease with loss of pyramidal neurons and disconnected glycine-NMDA receptor activation.

Analysis of Variance↗