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MK-801 impedes the acquisition of a spatial memory task in rats.

Several studies have reported that MK-801 impairs the acquisition of various learning and memory tasks, while others suggest that MK-801 may interfere with performance rather than having a specific effect on memory. To characterize further the effects of MK-801 on learning and memory, MK-801 (0.05 mg/kg, SC) was administered prior to or immediately after learning trials in a trial-independent water maze task. Since MK-801 may affect nonassociative variables that may influence learning and memory, motor activity and general reactivity measures were also determined for 0.0125, 0.025, or 0.05 mg/kg of MK-801 administered SC. Since MK-801 may also be used to treat children with epilepsy, we investigated the possible persistent cognitive effects on neonates. MK-801 (0.02 mg/kg, SC) was administered at postnatal days 9-15 and tested in the same task as above starting at day 36 of age. There were no persistent effects of neonatal treatment. However, in adult rats, MK-801 impaired the acquisition of the water maze task but did not affect performance during a recall task in the same apparatus. At doses affecting learning, there were no effects on motor activity or general reactivity in adult rats. These results are consistent with the conclusion that MK-801 interferes with acquisition of spatial learning in the rat.

Aging

Can age-related deficits in spatial memory be attenuated through the use of verbal coding?

In a sequential mental rotation task, women of three age groups (18-28, 50-60, and 70-80) viewed semi-abstract figures which were rotated in the picture plane. To investigate the effects of verbal mediation, each figure was presented under one of four labeling conditions. Errors increased as a function of age. Meaningful labels were beneficial in decreasing errors for the older subjects. Reaction time results generally replicated earlier studies, but there were indications that some women in the oldest group might have used strategies other than mental rotation. Results suggest that possible age related deficiencies in spatial abilities may be compensated for by greater use of verbal mediation.

Adolescent

Locomotion, active choice, and spatial memory in children.

In two studies, children between 4 and 6 years old were tested on a radial search task requiring nonredundant sampling of eight identically labeled positions in a room. In the training phase (5 days), children made free choices by walking between positions, were passively transported in a pushchair, actively directed their own route from a pushchair, or were led on foot to positions selected by the experimenter. When tested (whether walking or directing while seated in a pushchair), children who had either walked independently or directed the experimenter while being pushed performed competently; those led on foot without spatial choice performed almost as well. Only the children who had neither independent locomotor experience nor autonomous choice performed very poorly. The results are related to neurobiological models of spatial cognition and may have implications for the transportation of children with mobility problems.

Child, Preschool

Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotinic cholinergic antagonist, on spatial memory in rats.

The effects of both systemic and intracerebroventricular administration of mecamylamine, a nicotinic antagonist, were tested on the Morris water maze performance of rats. In experiment 1, mecamylamine (0, 3, and 10 mg/kg, IP) was administered before daily training sessions on the Morris water maze, a task in which rats use environmental cues to learn the location of an invisible escape platform in a large pool of water. The escape latencies of rats given the higher dose of mecamylamine were significantly longer than the latencies of rats given either saline or the peripherally-acting nicotinic antagonist hexamethonium (10 mg/kg). Analysis of search patterns during a free swim trial conducted in the absence of an escape platform confirmed the disruptive effects of the higher dose of mecamylamine. Similar drug effects were not observed when these rats were trained to a visible platform, and mecamylamine did not affect the retrieval of spatial information in well-trained rats. In experiment 2, similar effects were observed with ICV administration of mecamylamine (0, 10, 30, and 100 micrograms). The two higher doses increased escape latencies during the last day of place training and all three doses significantly impaired performance on a free swim. No significant effects were noted on subsequent training to a visible platform, and only the highest dose marginally impaired the retrieval of spatial information in well-trained animals. Thus, mecamylamine appears to impair the acquisition of spatial information in the Morris water maze but does not affect retrieval of previously acquired spatial information at comparable doses.

Animals

Pigeons' spatial memory: III. Effect of distractors on delayed matching of key location.

The effect of distractors on pigeons' delayed matching of key location was investigated. Baseline trials began with a "ready" stimulus (brief operation of the grain feeder). Then one (randomly chosen) key from a three-by-three matrix was lit briefly as the sample. After a short delay (retention interval) the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample (correct comparison) produced grain reinforcement, whereas a peck to the other key (incorrect comparison) produced only the intertrial interval. In Experiment 1, a houselight distractor, presented during either the sample, retention interval, or choice phases of the trial, had little if any effect on accuracy of matching key location. In Experiment 2, one of three types of spatial stimuli was interpolated during the retention interval, or the interval was blank as during baseline trials. The three stimuli were: the sample (correct comparison) location for that trial, the incorrect comparison location for that trial, or one of the seven unused locations for that trial. Relative to blank trials, accuracy improved slightly on sample-interpolated trials, decreased slightly on unused location-interpolated trials, and decreased considerably on incorrect comparison-interpolated trials. In Experiment 3, retention intervals were blank or had one of six types of interpolation: the sample, the incorrect comparison, two presentations of the sample, two presentations of the incorrect comparison, the sample followed by the incorrect comparison, or the incorrect comparison followed by the sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Spatial memory in aged rats: population heterogeneity and effect of levocarnitine acetyl.

The existence in a population of aging rats of classes that display a different performance in the Morris water-maze test was investigated by cluster analysis procedure. These classes identified at 18 months of age showed a different response to levocarnitine acetyl and had a different behavioral profile when tested at 25 months of age. These findings demonstrate the need for an alternative interpretation of variability in animal populations as measured by the standard statistical analyses. The data analysis strategy we propose here will allow for the use of variability as a useful source of information.

Acetylcarnitine

Landmark learning and visuo-spatial memories in gerbils.

The aim of this study is to understand what a rodent (Meriones unguiculatus) learns about the geometrical relations between a goal and nearby visual landmarks and how it uses this information to reach a goal. Gerbils were trained to find sunflower seeds on the floor of a light-tight, black painted room illuminated by a single light bulb hung from the ceiling. The position of the seed on the floor was specified by an array of one or more landmarks. Once training was complete, we recorded where the gerbils searched when landmarks were present but the seed was absent. In such tests, gerbils were confronted either with the array of landmarks to which they were accustomed or with a transformation of this array. Animals searched in the appropriate spot when trained to find seeds placed in a constant direction and at a constant distance from a single cylindrical landmark. Since gerbils look in one spot and not in a circle centred on the landmark, the direction between landmark and goal must be supplied by cues external to the landmark array. Distance, on the other hand, must be measured with respect to the landmark. Tests in which the size of the landmark was altered from that used in training suggest that distance is not learned solely in terms of the apparent size of the landmark as seen from the goal. Gerbils can still reach a goal defined by an array of landmarks when the room light is extinguished during their approach. This ability implies that they have already planned a trajectory to the goal before the room is darkened. In order to compute such a trajectory, their internal representation of landmarks and goal needs to contain information about the distances and bearings between landmarks and goal. For planning trajectories, each landmark of an array can be used separately from the others. Gerbils trained to a goal specified by an array of several landmarks were tested with one or more of the landmarks removed or with the array expanded. They then searched as though they had computed an independent trajectory for each landmark. For instance, gerbils trained with an array of two landmarks were tested with the distance between two landmarks doubled. The animals then searched for seeds in two positions, which were at the correct distance and in the right direction from each landmark.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Early post-natal administration of 5,7-dihydroxytryptamine destroys 5-HT neurons but does not affect spatial memory.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) may play an important role in learning and memory. It has also been suggested that 5-HT abnormalities may mediate some aspects of the cognitive disorders associated with Korsakoff syndrome and Alzheimer's Disease. The effect of intracisternally applied 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) on learning and memory in rodents was evaluated. Three-day-old rat pups were treated with pargyline (40 mg/kg, i.p.) followed by 5,7-DHT (50 micrograms/pup) and returned to the dam for a month. At 75 days of age, rats were tested on a learning set problem in the Morris water maze for 5 days followed by 30 days of testing in a 12-arm radial maze with 8 of the 12 arms baited. In the Morris water maze, the latency to locate the hidden platform did not differ significantly for 5,7-DHT treated and control rats (F less than 1.0). Similarly, 5,7-DHT treated rats performed comparably to controls on the 12-arm radial maze (F less than 1.0). At 106 days of age the assay of tryptophan hydroxylase activity in the dorsal raphe nuclei and hippocampus showed marked reduction (86%, 78%, respectively) in 5,7-DHT treated animals compared to vehicle injected controls. Immunocytochemical analysis was consistent with the biochemical results. In 5,7-DHT treated animals there was severe loss of neurons that bind 5-HT antibody in the dorsal and medial raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine

Differential effects of frontal-lobe lesions on cognitive estimation and spatial memory.

Patients with unilateral frontal- or temporal-lobe excisions and normal control subjects were tested on the recall of objects and of their location in an array. An incidental-learning situation was used, in which the task was presented as a test of the ability to estimate the prices of the objects. Patients with right frontal-lobe lesions were the only group impaired on price estimation, but a correlation was obtained between error-score in price estimation and lesion-size for the left frontal-lobe group. In contrast to patients with extensive right hippocampal excisions, both frontal-lobe groups were accurate on location-recall when tested immediately and again 24 hr later.

Adolescent

Spatial memory processing during hippocampal long-term potentiation in rats.

It was investigated in rats whether hippocampal long-term potentiation (LTP) influences working and/or reference memory processing in the radial maze. After preliminary training to an intermediate level of performance, experimental subjects received a series of high-frequency trains of electrical pulses applied to the right perforant path. Two control groups were adopted in order to control for possible effects of stimulation plus operation, and operation alone, respectively. Twenty-four hours after the experimental treatment, animals were administered one trial of radial maze training. This sequence of hippocampal stimulation and radial maze training was replicated 15 times. After a retention interval of 2 months, one radial maze trial was presented on each of 3 consecutive days. The analysis of field potential data showed that periodic LTP stimulation produced a state of hippocampal LTP confined to the initial portion of the acquisition phase. Evaluation of radial maze data revealed a marginal improvement of working memory performance in the experimental group during the rising phase of hippocampal LTP.

Animals