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At least 433 records · Page 24Linked to original sources

PubMed1994

Spatial learning and noradrenaline content in the brain and periphery of young and aged rats.

The present experiment studied whether a dysfunction of the noradrenergic neurons is related to spatial learning impairment by investigating the levels of noradrenaline in the brain and periphery as well as the acquisition of water maze task in saline-pretreated young rats, in noradrenergic neurotoxin (DSP-4)-pretreated young rats and in saline-pretreated aged rats. Aged rats, which had an increased escape latency onto the hidden platform, revealed a decreased noradrenaline content in the heart, but not in the hippocampus, striatum, or hypothalamus, whereas DSP-4-pretreated rats had decreased noradrenaline content in the brain; the acquisition of water maze task was not impaired. These results suggest that the peripheral noradrenergic system can show age-related changes different from those in the central noradrenergic system, and they failed to provide support for the hypothesis that decreased activity of the central noradrenergic nerves is related to impairment in the acquisition of the water maze task.

Aging↗

PubMed2005

The effects of carbenoxolone on spatial learning in the Morris water maze task in rats.

BACKGROUND: High-frequency oscillations (ripples) are proposed to be involved in memory consolidation. Ripple oscillations persist in the absence of chemical synaptic transmission and inhibitors of gapjunctions were shown to block high-frequency oscillations in hippocampal slices. In this study we investigated the effects of carbenoxolone, as a gap-junction blocker, on spatial learning in the rat. Cognitive performance was assessed using the Morris water maze (MWM). MATERIAL/METHODS: Adult male rats were bilaterally cannulated into the CA1 region of their hippocampus. Carbenoxolone (1.23, 2.46, 4.92 microg/side), scopolamine (3 microg/side), and saline were injected through the cannulas before 4 consecutive training trials and one test trial that conducted 24 h after the training trials with the platform removed. RESULTS: The results showed that carbenoxolone could significantly reduce the percentages of time spent, distance traveled, and entry into Q2 (the target quadrant) compared with the control group. The carbenoxolone group failed to use a selective search strategy during the final test trial, in which the platform was removed. CONCLUSION: The results of this study suggest that carbenoxolone as a gap-junction channel blocker can decelerate the learning performances of rats in a spatial memory task, such as the MWM, that requires the integrity of the hippocampus.

Animals↗

PubMed1999

S 15535, a benzodioxopiperazine acting as presynaptic agonist and postsynaptic 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine.

1 The effect of S 15535 (4-benzodioxan-5-yl)1-(indan-2-yl)piperazine), an agonist at presynaptic and antagonist at postsynaptic 5-HT1A receptors, on the impairment of spatial learning caused by intrahippocampal scopolamine in a two-platform spatial discrimination task was studied. 2 Scopolamine (4.0 microg microl-1), injected bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. 3 Administered subcutaneously 30 min before each training session, S 15535 1.0 (but not 0.3) mg kg-1 did not modify choice accuracy but prevented its impairment by intrahippocampal scopolamine. 4 WAY 100635, a 5-HT1A receptor antagonist, injected into the dorsal raphe at 1.0 microg 0.5 microl-1 5 min before scopolamine, had no effect on choice accuracy and latency or errors of omission and did not modify the effect of scopolamine but completely antagonized the effect of S 15535 (1.0 mg kg-1) on scopolamine-induced impairment of choice accuracy. 5 The results confirm a previous report (Carli et al., 1998) that stimulation of presynaptic 5-HT1A receptors in the dorsal raphe counteracts the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. 6 Drugs that stimulate action on presynaptic 5-HT1A receptors, such as S 15535 and other partial 5-HT1A receptors agonists, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.

Animals↗

PubMed2001

Long-term effects of neonatal MK-801 treatment on spatial learning and cortical plasticity in adult rats.

RATIONALE AND OBJECTIVES: The long-term effects of neonatal treatment with MK-801 on spatial learning and cortical plasticity were investigated in adult rats. METHODS: Rat pups were injected twice daily with MK-801 (0.1 mg/kg) on postnatal days 7-19, participated in water maze testing between postnatal days 90 and 102, and were then studied electrophysiologically. RESULTS: Treatment with MK-801 in such a low dose resulted in a very slight impairment of performance in the water maze task, but not in the visual cue response. Besides the slight learning impairment, the electrophysiological study revealed a reduction in the capacity for plasticity in the primary motor cortex of the treated animals, which was pronounced in the controls. CONCLUSION: The study demonstrates that even a slight impairment in learning and memory function may be accompanied by a cortical plasticity deficiency that is detectable electrophysiologically.

Animals↗

PubMed2006

High fat/refined carbohydrate diet enhances the susceptibility to spatial learning deficits in rats exposed to intermittent hypoxia.

BACKGROUND: Intermittent hypoxia during sleep (IH), as occurs in sleep disordered breathing (SDB), induces spatial learning deficits associated with regulation of transcription factors associated with learning and memory in the hippocampal CA1 region in rats. high fat refined carbohydrate diet (HF/RC) can induce similar deficits and associated changes in signaling pathways under normoxic conditions. METHODS: Sprague-Dawley adult male rats were fed either with (HF/RC) or low fat/complex carbohydrate diet (LF/CC) starting at post-natal day 30 for 90 days, and were then exposed for 14 days during light phase (12 h/day) to either normoxia (RA) or IH (21% and 10% O2 alternations every 90 s). Place-training reference memory task deficits were assessed in the Morris water maze. Total and ser-133 phosphorylated CREB were assessed in different brain regions by Western blotting and immunostaining in rats exposed to normoxia or IH and to LF/CC or HF/RC. RESULTS: Substantial decreases in CREB phosphorylation occurred in CA1 but not in motor cortex following either IH, HF/RC, and HF/RC + IH. Place-training reference memory task deficits were observed in rats exposed to IH and to HF/RC, and to a much greater extent in rats exposed to HF/RC + IH. CONCLUSIONS: Nutritional factors alter recruitment of transcription factors, possibly via oxidative-related pathways, and modulate the vulnerability of the CA1 region of the hippocampus to the episodic hypoxia that characterizes SDB, thereby enhancing neurocognitive susceptibility in SDB patients.

Animals↗

PubMed1987

Spatial learning in the rat: impairment induced by the thiol-proteinase inhibitor, leupeptin, and an analysis of [3H]glutamate receptor binding in relation to learning.

Rats were given continuous intraventricular infusion of saline or the thiol-proteinase inhibitor leupeptin, via subcutaneously implanted osmotic minipumps, while being trained on a spatial learning water task using spaced trials. Leupeptin caused overnight forgetting during training, but performance eventually reached asymptote in both groups. A retention test conducted 48 h later to assess spatial memory revealed no significant group differences, but did cause, in saline-treated rats only, a disruption of subsequent retraining back to the correct spatial location. The groups showed no differences in Cl-dependent [3H]glutamate receptor binding to hippocampal or entorhinal cortex membranes subsequent to training. In a second experiment, normal rats trained on the same task also showed no differences in Cl-dependent [3H]glutamate binding relative to rats exposed to the water task but given random spatial position training and handled controls. The results are discussed in relation to the hypothesis of Lynch and Baudry (Science (1984) 224, 1057-1063) that a calcium-dependent thiol proteinase is involved in memory formation through its ability to modify glutamate receptor distribution and dendritic spine shape.

Animals↗

PubMed1996

Spatial learning and memory deficits after telencephalic ablation in goldfish trained in place and turn maze procedures.

The present work investigated whether the fish telencephalon is involved in spatial learning based on place strategies in a manner similar to mammalian hippocampus. Goldfish were trained in a 4-arm maze in a room with relevant spatial cues. Sham and to-be-ablated subjects were trained in each of 4 experimental procedures designed as follows: place, turn, place-turn, and control. After acquisition, complete ablations of both telencephalic hemispheres for the experimental groups were carried out. The results showed that ablation exclusively impaired performance in animals using place strategies; in these, accuracy fell to chance level during both postsurgery retraining and reversal periods. In the other groups, ablation of the telencephalon did not induce any significant deficit. These results suggest that the fish telencephalon plays a crucial role in complex place learning.

Animals↗

PubMed1993

Levemopamil reduces spatial learning deficit following transient occlusion of common carotid arteries in normotensive rats.

The effect of the calcium channel blocker and 5-HT2 antagonist levemopamil on spatial learning impairment of rats subjected to transient bilateral clamping of carotid arteries (BCCA) was investigated. In addition, the acute effect of BCCA on local cerebral blood flow was measured in the presence and absence of levemopamil in a separate group of rats. Pretreatment with levemopamil prevented the BCCA-induced increase in escape latency during the test trials and ameliorated the BCCA-induced decrease in spatial bias during a probe trial. Under these experimental conditions, local cerebral blood flow fell to near ischaemic values in all mid- and forebrain regions during occlusion of the carotid arteries. However, pretreatment with levemopamil affected the BCCA-induced blood flow changes only in one brain area of 34 investigated. The present data suggest that pretreatment with levemopamil reduces impairment in spatial behaviour and that this effect seems not related to the compound's cerebral vasodilatory action, but to direct neuronal mechanisms.

Animals↗

PubMed2005

Subordinate male mice show long-lasting differences in spatial learning that persist when housed alone.

In the wild, house mice live in social groups, whereas in the laboratory male mice are often singly housed. Environmental enrichment such as that provided by social housing has been argued to improve the cognitive performance of laboratory animals in experimental tests. The aim of the present study was to test the cost of aggressive social interactions on learning in male CD-1 mice. We found that subordinate mice from more aggressive dyads showed spatial learning impairment, measured as alternation on a T-maze. Learning impairments in subordinates have hitherto been presumed attributable to the animals' exposure to, and relative standing within, the social group. By contrast, the impairment we observed could not have been the result of recent social defeat because it persisted weeks later when the mice were housed alone. Elevated urinary corticosterone predicted later subordination, though paradoxically these abnormally high levels were reduced by pair housing.

Analysis of Variance↗

PubMed1984

Facilitation of generalization performances in spatial learning problems by posttrial stimulation of the mesencephalic reticular formation.

The effects of low posttrial stimulation of the mesenphalic reticular formation (MRF) on spatial learning problems were studied in two consecutive stages. First, the performances of stimulated (S) and no-stimulated (NS) subjects were assessed in a reconvergent three-arm maze. Secondly, the same animals were tested in a generalization paradigm, since they had to solve a similar task in a radial four-arm maze, each group being divided into newly stimulated (S-S, NS-S) or no-stimulated (S-NS, NS-NS) subjects. In the first experiment, no differences were found between the acquisition processes of groups S and NS. Conversely, in the second experiment, previously stimulated animals (S-S and S-NS) showed better generalization of the experimental rule. The results are discussed in terms of preservation of the neural activity after the early MRF stimulation. From a functional point of view, our data indicate that an enhancement of the neural activity during acquisition facilitates not only a high accessibility of memories concerning the experimental rule in a subsequent similar situation but also the capability to apply a previously elaborated response system in a more complex situation.

Animals↗

PubMed2004

The effect of chronic restraint stress on spatial learning and memory: relation to oxidant stress.

The aim of this study was to investigate the effect of chronic restraint stress (RS) on spatial learning and memory. Fifty healthy male Wistar rats, aged three months were used. They were equally divided into five groups--C: Control, W: Water Maze, CS-1: Restrained for 21 days (1 h/day) + water maze protocol following stress period, CS-2: Restrained for 28 days (1 h/day) + water maze protocol during last 7 days of stress period, CS-3: Restrained for 21 days and allowed to recovery for 7 days (1 h/day). Corticosterone levels were higher in all stress groups than in C and W groups. Nitrite levels of frontal cortex and hippocampus were found to be elevated in chronic stress groups with respect to C and W groups. Thiobarbituric acid reactive substances (TBARS) of both tissues were increased significantly in CS1 and CS2 groups compared with C, W, and CS3 groups. Escape latencies of CS1 and CS2 groups were longer than those of the W group on each day of acquisition. In transfer test, CS1 and CS2 groups stayed significantly shorter in target quadrant according to the W group. Significant correlations between corticosterone and either nitrite or TBARS of hippocampus and frontal cortex were found. Both acquisition and memory performances were negatively correlated with plasma corticosterone level, nitrite, and TBARS levels of hippocampus and frontal cortex. The results of this study suggest that stress-induced lipid peroxidation may affect the acquisition and memory performances.

Analysis of Variance↗

PubMed1999

American ginseng extract reduces scopolamine-induced amnesia in a spatial learning task.

OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits.

Animals↗

PubMed2005

PS1 knockin mice with the Japanese I213T mutation: effects on exploratory activity, motor coordination, and spatial learning.

Knockin (KI) mice with a PS1/I213T mutation were compared to wild-type controls on the SHIRPA primary screening battery and for exploratory activity, motor coordination, and spatial learning. By comparison to non-transgenic controls, PS1/I213T KI mice had retarded acquisition of place learning in the Morris water maze without being impaired in the probe trial and in the visible platform subtest. PS1/I213T KI mice were more likely to display whole-body startle to an auditory stimulus and a tighter grip on a horizontal grid. PS1/I213T KI mice also had fewer enclosed arm entries in the elevated plus-maze, but did not differ from controls in open-field, photocell actimeter, and T-maze spontaneous alternation tests. No intergroup difference was seen in three motor coordination tests. The dissociation between hidden and visible platform versions in the water maze is consistent with the hypothesis that elevated Abeta42 concentrations cause cognitive disturbances.

Acoustic Stimulation↗

PubMed2003

Selective neurodegeneration of hippocampus and entorhinal cortex correlates with spatial learning impairments in rats with bilateral ibotenate lesions of ventral subiculum.

Rats with bilateral ibotenic acid lesions of ventral subiculum were tested in an eight-arm radial maze task for spatial learning and memory functions. The performance of the lesioned rats was severely impaired relative to control rats in both acquisition and retention of the spatial task. Following subicular lesions, profound neurodegeneration of the CA1 and CA3 sub sectors of hippocampus and entorhinocortical layers I, II, III, V and VI was observed. These results support the concept that neurons in the ventral subiculum are a part of the neural network along with the above neurons, which could be involved in the processing of spatial information.

Animals↗

PubMed2000

Exercise influences spatial learning in the radial arm maze.

Previous studies indicate that the hippocampus is active during exercise, and that neurotrophin expression, receptor density, and survival of dentate gyrus granule cells in the hippocampus can be modified by moderate voluntary exercise. The present study was designed to test the consequences of voluntary exercise on a hippocampal-related behavior. Exercising and control rats were tested on the standard and delayed nonmatch-to-position (DNMTP) version of the eight-arm radial maze, both of which are sensitive to hippocampal damage. Voluntarily exercising rats ran in running wheels attached to their home cage for 7 weeks prior to and throughout testing, and took 30% fewer trials to acquire criterion performance than sedentary controls. Both groups spent the same average time per arm. Once the eight-arm maze had been learned to criterion, group differences were not apparent. Exercise can facilitate acquisition of a hippocampal-related spatial learning task, but does not affect performance following acquisition. Further work will be necessary to link these effects to hippocampal-related variables shown to be influenced by exercise.

Analysis of Variance↗

PubMed1995

Modulation of carbon monoxide production and enhanced spatial learning by tin protoporphyrin.

Endogenous carbon monoxide (CO), produced by haem oxygenase (HO), may play a role in hippocampal long-term potentiation (LTP). Its role in learning and memory in intact animals is less well known. Tin protoporphyrin (Sn-PP; 25 mg kg-1, i.p.) effectively but transiently inhibited HO activity in brain homogenates, and improved acquisition in the Morris water maze. Locomotor activity was unaffected, indicating a behavioural specificity of the learning effect. The analogue zinc protoporphyrin (25 mg kg-1, i.p.), which does not pass the blood-brain barrier, did not affect learning. If the observed memory effect is related to inhibition of HO, the role of CO in spatial learning may be different from that suggested by LTP studies.

Animals↗

PubMed1992

The effects of alpha-2 adrenoceptor antagonist, atipamezole, on spatial learning in scopolamine-treated and aged rats.

In order to study whether noradrenergic drugs improve age-related cognitive dysfunctions the present experiments investigated whether atipamezole, a selective and specific alpha-2 antagonist, improves spatial learning impairment due to cholinergic blockade (scopolamine 0.8 mg/kg) or aging in rats. Previously, it has been shown that atipamezole dose-dependently (0.03-3.0 mg/kg) increases the turnover of noradrenaline in rat brain. According to the present results, atipamezole (0.1, 0.3, 0.6 mg/kg) did not affect spatial learning/memory when assessed in a free swim trial of the water maze task in control rats. Furthermore, atipamezole (0.1, 0.6 mg/kg) did not improve learning deficit in scopolamine treated young rats. Higher doses (greater than or equal to 1.0 mg/kg) of atipamezole could not be tested, because they induce floating behaviour in rats. In aged rats, which were screened to be impaired in the initial acquisition of the water maze task, 0.3 mg/kg atipamezole impaired further learning of this task. Because previous studies suggest that age-related learning impairment in the water maze may be, at least partly, due to a cholinergic deficit, the present results suggest that atipamezole which increases the release of noradrenaline in brain does not alleviate this learning deficit.

Adrenergic alpha-Antagonists↗

PubMed1996

A comparison of the effects of frontal cortical and thalamic lesions on measures of spatial learning and memory in the rat.

Two experiments were conducted to compare the effects of radiofrequency lesions of thalamus and frontal cortex on three measures of spatial learning and memory: delayed non-matching to sample (DNMTS), radial arm maze with imposed delays, and serial reversal learning. Thalamic lesions were aimed at the lateral internal medullary lamina (L-IML) and cortical lesions at the projection areas of the mediodorsal nucleus along the medial wall (MW) and dorsal to the rhinal sulcus (RS) in frontal cortex. In Experiment 1 rats were trained on DNMTS prior to surgery. After recovery, rats with MW lesions showed persistent deficits on DNMTS that were significantly greater than for RS lesions. The deficits observed in MW lesioned animals were comparable to the effects of L-IML lesions on this task that have been described in previous studies. In Experiment 2 animals were trained to perform the radial arm maze task prior to treatment. After recovery, animals with L-IML lesions were impaired on the radial arm maze and on subsequent acquisition of the serial reversal task. Rats with RS and MW lesions showed transient impairments on the radial arm maze task, but otherwise performed as well as controls on both these tasks.

Animals↗