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PubMed2000

Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains.

Correlations between the densities of ionotropic glutamate, GABA(A), and serotonin binding sites in the hippocampus of seven inbred mouse strains and strain-specific learning capacities in two types of maze were studied. Binding site densities were measured with quantitative receptor autoradiography. Learning capacities were determined in a water maze task as well as in spatial and nonspatial versions of an eight-arm radial maze. The densities of most binding sites differed significantly between the strains in the subfields of Ammon's horn (CA1 and CA3) and the dentate gyrus, except for serotonin binding sites in CA1. By comparing the different strains, significant receptor-behavioral correlations between the densities of the GABA(A) receptors and the activity-dependent behavior in the water maze as well as the spatial learning in the radial maze were found. The densities of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (AMPA) and kainate receptors correlated positively with learning capacity in the spatial eight-arm radial maze. We conclude that hereditary variations mainly in AMPA, kainate, and GABA(A) receptor densities are involved in behavioral variations in spatial and nonspatial learning tasks.

Analysis of Variance↗

PubMed2006

Effects of Ginkgo biloba administered after spatial learning on water maze and radial arm maze performance in young adult rats.

Ginkgo biloba is reported to improve learning and memory in animals. However, many studies do not directly test the effects of Ginkgo on memory because the drug is administered during the learning phase of the experiments. In this study, we examined the effect of 10 mg/kg, 20 mg/kg, or 40 mg/kg G. biloba extract on spatial memory by administering the drug in the interval between training and testing. Rats were tested for long-term reference memory retention in the radial arm maze and in the Morris water maze during daily probe trials in which the hidden platform was removed. G. biloba had no effect on reference memory in either the water maze or radial arm maze. To test short-term working spatial memory using the radial arm maze, animals were removed after receiving the reward from 4 of the 8 arms and were returned to complete the maze 2 h later. While Ginkgo had no effect on working memory, over time animals exposed to Ginkgo learned task better than control animals. Thus, Ginkgo appears to enhance neither short-term working memory nor long-term reference memory, but it may promote learning of spatial information.

Animals↗

PubMed1997

Spatial disorientation blocks reliable goal location on a plus maze but does not prevent goal location in the Morris maze.

Cue control in spatial learning was investigated in a plus maze and a Morris maze. Rats transported in opaque containers with prior rotation to a plus maze, but not a Morris maze, could not find a goal defined by external cues. Rats transported in clear containers without rotation found the goal in both mazes. In the Morris maze, goal location was readily relearned following cue removal by rats in clear containers but not by rats in the opaque/rotation group. B. L. McNaughton et al.'s (1996) theory that during spatial learning sensory information is bound to preconfigured internal maps in the hippocampus, whose metric is self-motion and whose orientation depends on input from an inertial based head direction system, may explain this study's findings.

Animals↗

PubMed2005

Anxiogenic profile of AM-251, a selective cannabinoid CB1 receptor antagonist, in plus-maze-naïve and plus-maze-experienced mice.

The notoriously inconsistent effects of cannabinoids on anxiety-like behaviour may be explained by recent research on CB1 receptor knockout (CB1-KO) mice suggesting that cannabinoids exert bidirectional effects via the CB1 receptor (anxiolysis) and a novel rimonabant-sensitive neuronal cannabinoid receptor (anxiogenesis). This hypothesis is supported by the anxiogenic-like profile of AM-251, an analogue of rimonabant that is a potent and selective CB1 receptor antagonist but which, unlike rimonabant, has no activity at the novel receptor. As we have previously shown that rimonabant reduces anxiety-like behaviour in test-experienced animals only, the current study assessed the effects of AM-251 (1.5-3.0 mg/kg) in male Swiss-Webster mice that were either plus-maze-naïve or had been exposed undrugged to the apparatus 24 h prior to testing. Results confirmed that prior maze experience per se significantly increases behavioural indices of anxiety without altering measures of general activity. In maze-naïve mice, the lower dose of AM-251 (1.5 mg/kg) significantly reduced % open-arm time and increased grooming while the higher dose (3.0 mg/kg) additionally reduced open-arm entries and total head-dipping, and increased closed-arm returns. These anxiogenic-like effects were observed in the absence of significant changes in general activity levels. Although AM-251 had a very similar profile in maze-experienced animals, significant drug effects on open-arm avoidance measures were precluded by experientially-induced changes in behavioural baselines (i.e. 'ceiling' effects). Nevertheless, AM-251 again significantly reduced total head-dipping and increased grooming (3.0 mg/kg) and, unlike effects in naïve animals, both doses markedly reduced time spent on the centre platform and increased time spent in the enclosed arms. Against a baseline of almost total open-arm avoidance, the pattern of behavioural change in maze-experienced mice would also be consistent with an anxiogenic-like action of AM-251. Data are discussed in relation to previous findings with rimonabant, the putative existence of a novel non-CB1 neuronal cannabinoid receptor and, more generally, the behavioural pharmacology of plus-maze 'trial 2'.

Analysis of Variance↗

PubMed1989

Effects of ketamine on tunnel maze and water maze performance in the rat.

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.

Animals↗

PubMed1996

Radial maze performance, open-field and elevated plus-maze behaviors in Fyn-kinase deficient mice: further evidence for increased fearfulness.

Fyn-deficient mice produced by inserting the beta-galactosidase gene (lacZ) into the fyn gene locus were tested in a radial maze, an open field and an elevated plus-maze. In the radial maze, the homozygous Fyn-deficient (fynz/fynz) mice showed no impairment in spatial learning, although they showed a stronger avoidance tendency for those arms located closer to the experimenter during pretraining (adaptation). In the open-field test, the fynz/fynz mice defecated more frequently in the bright condition than did the +/fynz mice, and they were less active during the first 10-min test period than the +/fynz mice. In addition, the temporal pattern of locomotor activity for fynz/fynz mice was altered by changing the illumination while the pattern for +/fynz mice remained relatively unchanged. Scores reflecting the fear-response in the elevated plus-maze were higher in the fynz/fynz mice. These results indicate that Fyn deficiency increased fear-response, but did not impair spatial learning in the radial maze. It is suggested that we should take account of effects of emotional factors in the learning experiment using mutant mice.

Animals↗

PubMed1997

Spatial delayed alternation of rats in a T-maze: effects of neurotoxic lesions of the medial prefrontal cortex and of T-maze rotations.

The medial prefrontal cortex (mPFC) is usually considered to be a brain area important for working memory processes. In rats this statement is evidenced by their diminished performance in delay-type tasks following mPFC damage, notably in spatial delayed alternation (SDA) in a T-maze. This study has addressed two questions. First, to examine whether the functional deficiency in SDA, observed in rats with (usually large) mPFC damage, can be ascribed to an anatomically defined subarea of mPFC, the dorsal anterior cingulate area (ACd). Small, bilateral, NMDA-induced lesions were made, restricted to the dorsal part of mPFC. The performance of such animals in a T-maze paradigm, using delays of 0 and 15 s, was compared with sham-operated animals. Although these small lesions resulted in an increased number of perseverative errors, this effect was not delay-dependent, and, moreover, by the end of the training group differences had disappeared. The second aim was to study whether or not spatial (extra-maze) cues are important for the performance of this task. This was achieved by subjecting the well-trained sham-operated animals to a series of systematic trial-to-trial variations in the position of the maze in the experimental room. These spatial manipulations severely impaired the performance of the SDA task, indicating that extra-maze information is required to solve this task. In animals with ACd lesions, subjected to the same manipulations, the deficiency was comparable to that of the sham-operated animals.

Animals↗

PubMedDate not supplied

Administration of D,L-fenfluramine to rats produces learning deficits in the Cincinnati water maze but not the Morris water maze: relationship to adrenal cortical output.

Fenfluramine (FEN) is an amphetamine derivative with anorectic properties similar to amphetamine, but without the stimulatory or abuse potential. Administration of FEN produces an immediate release of serotonin as well as inhibits reuptake; ultimately FEN produces a decrease in serotonin stores in the central nervous system. We have previously shown that the administration of FEN to rats results in increased adrenal cortical hormones under resting conditions, without simultaneous elevations in adrenocorticotropin hormone (ACTH). We hypothesized that the adrenal output would be altered following stress and that the altered adrenal output would affect learning and memory, since the adrenal hormones influence learning and memory capability. In this series of experiments, we administered D,L-FEN (15 mg/kg) four times every 2 h on a single day to rats and investigated the effect on hormonal output following forced swim and the effect on sequential learning in the Cincinnati water maze and spatial learning in the Morris maze beginning 3 days after FEN administration. Animals that received FEN had increased corticosterone and aldosterone titers following forced swim relative to control animals, although no differences in ACTH or testosterone were noted. Animals exposed to FEN had lasting deficits in the Cincinnati water maze but not in the Morris water maze, regardless of testing order. These deficits in the Cincinnati water maze appear to be mediated by the elevation in adrenal output since adrenalectomy abolished the effect of FEN. Corticosterone levels were shown to be elevated during the behavioral testing period in animals exposed to FEN.

Adrenal Cortex↗

PubMed2000

[The maze operation--surgical therapy of chronic atrial fibrillation: modification to mini-maze operation].

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia. However, its precise electrophysiologic mechanism is still not well understood. Chronic symptomatic atrial fibrillation resistant to medical therapy can successfully be treated by the Maze III procedure (M III). Several publications are dealing with alternative surgical techniques. This study describes technique and midterm results of a Mini-variant (Mini) of the Maze III procedure. METHODS: During a 48-month period we performed either a M III (group I = 7 patients) or a Mini-Maze operation (group II = 65 patients) in 33 males and 39 females with chronic symptomatic atrial fibrillation and additional cardiac pathology. Patients were controlled 4.0 +/- 1.8 months (group I) respectively 3.6 +/- 0.8 months (group II) (NS) and 16.75 +/- 2.5 months (group I) respectively 13.2 +/- 1.9 months (group II) (NS) after operation by means of thorough electrophysiological assessment, right heart catheterization, MRI, echocardiography, stress-ECG and 24 h-ECG. RESULTS: There was no significant difference between the two groups with regard to sex, age and duration of AF. Echocardiographic left atrial diameter (LAD) was 75 +/- 11 mm in group I and 65 +/- 8 mm in group II (p = 0.002). Whereas right atrial diameter was 62 +/- 8 mm in group I and 57 +/- 7 mm in group II (NS). Perioperative data (n = 72): Aortic cross clamp time was 127 +/- 40 min in group I and 87 +/- 22 min in group II (p = 0.0002). Cardiopulmonary bypass time was 185 +/- 71 min in group I and 137 +/- 42 min in group II (p = 0.01). Postoperative data I (first follow-up: n = 66): sinus rhythm (yes): 4/7 vs. 47/59 (NS); pacemaker (PM) in AAI mode (yes): 1/7 vs. 3/59 (NS); inducible atrial fibrillation (yes): 2/7 vs. 5/59 (NS); Bradycardie Tachycardie Syndrome with the need of PM implantation 0/7 vs. 4/59 (NS). Postoperative data II (second follow-up: n = 55): sinus rhythm (yes): 5/7 vs. 34/48 (NS); PM in AAI mode (yes): 0/7 vs. 4/48 (NS); Inducible atrial fibrillation (yes): 2/7 vs. 5/48 (NS); Bradycardia Tachycardia Syndrome with the need of PM Implantation 0/7 vs. 5/48. CONCLUSION: Midterm results are identical after M III and Mini. The Mini-Maze procedure is less complex compared to the Maze III procedure and there is a significant reduction of crossclamp and ECC times. We recommend the Mini especially for polymorbid patients and for those with poor left ventricular function.

Adult↗

PubMed2004

Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-maze.

The present study evaluated the effects of a single intrahippocampal administration of brain-derived neurotrophic factor (BDNF) on memory retention in a water maze. Adult rats were trained in a water maze (acquisition phase, day 1). Immediately after the last training trial subjects were injected in the right hippocampus with either BDNF (24 microg) or phosphate-buffered saline (1 microl). On day 2, all subjects were tested for memory retention in a probe trial and were subsequently tested for reversal learning. While no differences emerged in the probe trial, BDNF-treated subjects showed a shorter latency and a shorter path length to reach the platform during the reversal phase. A significant difference in their "turn angle" and in their swim paths suggests that they might have used a different search strategy compared with controls. Moreover, all subjects also underwent an elevated-plus maze test. BDNF-treated-animals showed a clear tendency to spend a greater amount of time in the open arms and a significantly higher frequency of grooming behavior and of the stretched-attend posture in this maze area, but no differences in locomotion. Overall, these results indicate that administration of BDNF improves performance in a spatial memory task and has enduring effects on emotional behavior.

Animals↗

PubMed1994

Diazepam impairs place learning in native but not in maze-experienced rats in the Morris water maze.

Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.

Animals↗

PubMed2005

Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze Test".

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and incorporates a within-participants design to provide measures of location and object, working and reference memory. Healthy adult males and females (26 per group) were administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ test. Females made significantly fewer errors on this task than males. However, post hoc analysis revealed that the significant sex difference was specific to object, rather than location, memory measures. These were medium to large effect sizes. The findings raise the issue of task- and component-specific sexual dimorphism in cognitive mapping.

Adolescent↗

PubMed2005

Post insult enriched housing improves the 8-arm radial maze performance but not the Morris water maze task in ventral subicular lesioned rats.

The present study attempted to evaluate the efficacy of enriched housing conditions in promoting behavioral recovery following subicular lesion. Rats with bilateral ibotenic acid lesions of ventral subiculum were exposed to either enriched housing conditions or standard housing for 6 h daily for 10 days. The performance of the lesioned rats reared in standard housing conditions was severely impaired in both 8-arm radial maze and water maze tasks. Lesioned rats exposed to enriched housing showed behavioral recovery in the 8-arm radial maze but not in the water maze. Our study suggests the possibility that recovery may be based on the functional demand of spatial tasks and may require more appropriate environmental stimulation.

Animals↗

PubMed1997

Comparison of site specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin.

In this study we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on the water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study however was relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data does support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, it further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's Disease.

Animals↗

PubMed1996

Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin.

In this study, we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study was, however, relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is, by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data do support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, they further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's disease.

Animals↗

PubMed1997

Effects of repeated disorientation on the acquisition of spatial tasks in rats: dissociation between the appetitive radial arm maze and aversive water maze.

This study examined the effects of disorientation on the acquisition of different spatial reference memory tasks. In an appetitively motivated radial arm maze task in which 1 arm was consistently baited, rats that were disoriented before each trial were impaired in their ability to acquire the task relative to rats placed in a clear container and not disoriented. However, disoriented rats were able to learn a Morris water maze and a water version of the radial arm maze under similar training conditions, suggesting that the effects of disorientation may interact with the quality or quantity of motivation involved in a given task. These results suggest that appetitive and aversive spatial tasks are dissociable, and that any impairment that is due to disorientation is specific to the appetitive radial arm maze task.

Animals↗

PubMed1992

Differential ethanol intake in Tryon maze-bright and Tryon maze-dull rats: implications for the validity of the animal model of selectively bred rats for high ethanol consumption.

The search for a genetically based "animal model of alcoholism" has led to the creation of extensive research programs using various combinations of initial ethanol preference screening techniques and breeding methods to yield rodents with primary genetic differences that contribute to high or low ethanol preference. The present experiment examined the ethanol intake of the Tryon rat strain, which were bred for high and low maze learning scores. It was observed that the Tryon Maze Bright rats displayed an unprecedented affinity for ethanol with stable intakes between 12.7 and 13.7 g/kg per day and preference ratios exceeding 0.75 for ethanol concentrations ranging between 15 and 29%. The pattern of ethanol intake of the Tryon Maze Dull rats resembled the ethanol intake pattern of other, non-selectively bred strains of rats, approximately 2-3 g/kg of absolute ethanol at preference ratios between 0.11 and 0.28. The affinity for ethanol observed for the Tryon Maze Bright rats seems to exceed the reported consumption patterns of rat strains specifically bred for high ethanol consumption although the Tryon rats were selectively bred for variables that were seemingly unrelated to ethanol intake.

Alcohol Drinking↗

PubMed2005

Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks.

Hypoxia has generally been reported to impair learning and memory. Here we established a hypoxia-enhanced model. Intermittent hypoxia (IH) was simulated at 2 km (16.0% O2) or 5 km (10.8% O2) in a hypobaric chamber for 4 h/day from birth to 1, 2, 3, or 4 week(s), respectively. Spatial learning and memory ability was tested in the Morris water maze (MWM) task at ages of postnatal day 36 (P36)-P40 and P85-89, respectively, and in the 8-arm maze task at P60-68. The long-term potentiation (LTP), synaptic density, and phosphorylated cAMP-responsive element-binding protein (p-CREB) level in the hippocampus were measured in mice at P36 under the IH for 4 weeks (IH-4w). The results showed that IH for 3 weeks (IH-3w) and IH-4w at 2 km significantly reduced the escape latencies of mice at P36-40 in the MWM task with significantly enhanced retention, and this spatial enhancement was further confirmed by the 8-arm maze test in mice at P60-68. The improvement in MWM induced by IH-4w at 2 km was still maintained in mice at P85-89. IH-4w at 2 or 5 km significantly increased amplitude of LTP, the number of synapse, and the p-CREB level in the hippocampus of P36 mice. These results indicated that IH (4 h/day) exposure to neonatal mice at 2 km for 3 or 4 weeks enhanced mice spatial learning and memory, which was related to the increased p-CREB, LTP, and synapses of hippocampus in this model.

Age Factors↗