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PubMed1989

Low doses of atropine sulfate impair retention of a well-learned spatial task.

Retention of a well-learned spatial task was assessed in rats 10 minutes prior to, and 10, 20, 30, 40, and 50 minutes after treatment with 3, 10 or 30 mg/kg, iv, atropine sulfate or the equivalent volume of saline, iv. There was a variable dose effect for escape latency and choice accuracy measures of spatial retention. A relatively large dose of atropine sulfate (30 mg/kg, iv) significantly impaired choice accuracy and escape latency compared with the control group. Moreover, impairment in choice accuracy was observed with smaller doses of atropine sulfate (3, 10 mg/kg, iv) than have previously been shown to disrupt spatial retention.

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↗
PubMed1990

Atropine sulfate impairs selective parameters of performance in the Morris water maze.

Twelve rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze. Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the spatial task was assessed 30 min after treatment with 5, 25, 50, 75, or 100 mg/kg, ip, atropine sulfate or the equivalent volume of saline. There was a significant drug effect on escape latency, swim distance, swim speed and swim path measures of spatial performance. There was no significant drug effect on heading error; atropinized animals initially headed toward the escape platform over the first 12 cm of their swim path. However, treatment with atropine sulfate significantly disrupted the usual, direct swim path used to reach the hidden escape platform. Atropinized animals frequently swam a spiraled or looping pattern to locate the platform. We suggest that cholinergic blockade may significantly disrupt the processing of visual cues which rats use in place navigation tasks.

Animals↗
PubMed2002

Touch-screen system for assessing visuo-motor exploratory skills in neuropsychological disorders of spatial cognition.

A new computerised test adopting touch-screen technology has been developed to assess the visuo-motor exploration of extra-personal space. The test was derived from well-known paper-and-pencil cancellation tasks used widely in the diagnosis and quantitative assessment of unilateral spatial neglect (USN), a neuropsychological syndrome that is more frequent and severe after damage to the right cerebral hemisphere. A main component deficit of USN is the defective visuo-motor exploration of the side of space contralateral to the side of the lesion (contralesional), namely, in right-sided brain-damaged patients it occurs on the left side and vice versa. The computer-based paradigm consisted of a visuo-motor spatial exploratory task: the subjects were instructed to touch, in any order they wished, all the targets they detected on a computer touch-screen. This measured the time of occurrence and the spatial co-ordinates of each touch event and forwarded the data to the computer for storage; the computer provided feedback to the subject by 'tagging' the touched target. The paradigm allowed the calculation of accuracy and latency indexes and recorded the exploratory pathway taken by each subject. A pilot study was performed in ten normal subjects and 15 brain-damaged patients, with and without psychometric evidence of USN; the results showed that the equipment was able to provide quantitative indexes related to the spatial-temporal aspects of exploratory ability, which are useful for diagnostic purposes, and revealed significant differences between the controls and patients with USN: the overall average values of latency and crossing indexes increased in patients with USN, compared with the controls (latency from 0.77 to 1.90s; path crossing index from 7.0% to 59.5%), and the significantly negative USN patient latency gradient (-2.79 against a null control value) evidenced a worsening of performance towards the left side.

Aged↗
PubMedDate not supplied

Some antiepileptic compounds impair learning by rats in a Morris water maze.

In the present experiments, we investigated the effects of several commonly employed antiepileptic drugs on the performance of adult rats in a Morris water maze task. We found that phenytoin treatment produced the most deleterious performance impairments across all days of training, and that these performance deficits are not likely due to any general sensorimotor impairments. Carbamazepine had milder, but detectable negative effects, as carbamazepine-treated animals exhibited initial acquisition deficits, but rapidly achieved escape levels comparable to controls. In marked contrast, valproate and ethosuximide had no detectable effects on learning in the water maze. These results parallel previous findings in rats treated with these compounds and tested in an instrumental learning task, and are in general agreement with the human clinical literature. To the extent that one might wish to minimize learning deficits associated with maintenance on antiepileptic drugs, phenytoin is definitely not the treatment of choice, while valproate or ethosuximide are apparently much less disruptive.

Animals↗
PubMed2000

The hippocampus and flexible spatial knowledge in rats.

Lesions to the hippocampal system in rats result in a profound impairment of place or locale spatial learning although other learning strategies remain unaltered. The main objective of the present study was to investigate whether the spatial knowledge preserved in the hippocampal animals can be expressed flexibly under conditions different from those of the acquisition period. Rats with neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were trained to reach the goal arm in a four-arm plus-shaped maze using a constant starting arm. During the training a transparent plexiglas barrier divided the maze in two equal halves in such a way that the animals could only travel from the starting arm to the goal arm, not having access to the remaining 50% of the maze. After seven days of training, a transfer test was used in which the starting arms were the two arms from which the animals had not started during the training phase. Results indicated that the lesioned rats made significantly more errors than the control subjects. But the most interesting results revealed that the kind of error made by the lesioned animals was congruent with the turn that they had to make during the acquisition phase in order to access the goal arm (reinforced). These results suggest that when the hippocampus is damaged a preserved highly inflexible egocentric strategy is employed to solve the spatial problem.

Animals↗
PubMed2002

Effects of delta9-THC and WIN-55,212-2 on place preference in the water maze in rats.

RATIONALE: Cannabinoids such as delta(9)-tetrahydrocannabinol (delta(9)-THC) or WIN-55,212-2 (WIN-2) have psychoactive effects on cognition. As a result, the reinforcing properties of delta(9)-THC or WIN-2 may confound learning and memory tests with false negative results. It therefore seems advisable to assess the reinforcing properties of the drugs in the same behavioural model used for learning experiments. OBJECTIVE: We therefore developed conditioned place preference protocols in the open-field water maze and tested both delta(9)-THC (2 mg/kg) and WIN-2 (1 mg/kg and 3 mg/kg). Given that previous reports on cannabinoids have revealed conflicting data and that this was a novel behavioural test, we also tested the benzodiazepine receptor agonist diazepam (2.5 mg/kg). Some methodical refinements were appropriate in order to determine the behavioural strategy implemented by the animals. METHODS: All animals were injected intraperitoneally 30 min prior to training/testing. In experiment 1, male hooded Lister rats injected with drug were repeatedly placed on the drug-related platform and subsequently tested for place preference. In experiment 2, rats were trained to swim to the drug platform on drug days and to the vehicle platform on vehicle days. A series of probe trials was introduced to delineate what had been learned. Experiment 3 studied the effect of WIN-2 on spatial learning in the water maze. RESULTS: Neither WIN-2 nor delta(9)-THC induced place preference in the water maze. When trained in the swim procedure, however, WIN-2 was neutral, but Delta(9)-THC resulted in place aversion. Conversely, diazepam consistently produced place preference in both procedures. WIN-2 (3 mg/kg), however, produced a small learning deficit in the spatial water maze task. CONCLUSION: It appears that the reinforcing properties of delta(9)-THC and WIN-2 in the doses used here are different, despite them both being agonists at cannabinoid receptors within the central nervous system. The fact that delta(9)-THC may be aversively related to a particular context has implications for previous work reporting deficits in spatial learning.

Animals↗
PubMed2003

Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze.

RATIONALE: Neonatal administration of methamphetamine (MA) to rats from postnatal day (P) 11 to 20, but not from P1 to P10, produces lasting deficits in spatial learning and memory. The preweaning period of development in the rat corresponds to human third trimester hippocampal development and because of the increased use of MA in women of childbearing age, there is a greater likelihood that fetuses will be exposed to this drug. Development of the hippocampus is dependent upon many factors, including an optimal level of corticosterone (CORT). We have demonstrated that the CORT response of animals on P11 to MA is protracted relative to administration on P15 or P20. Interestingly, the P11 animals are still in the stress hyporesponsive period. OBJECTIVES: We postulated that because of the prolonged CORT response on P11, the effects of MA on spatial learning and memory may be confined to a shorter period of exposure. METHODS: Neonatal rats were administered MA (10 mg/kg) 4 times daily from either P11 to P15 or from P16 to P20, raised to adulthood and tested against animals only administered saline (SAL) from P11 to P20 for anxiety, swimming ability, and spatial learning and memory. RESULTS: Animals exposed to MA, regardless of exposure period, tended to be less anxious in the Zero maze relative to SAL animals. No differences were noted for swimming ability. Only animals exposed to MA from P11 to P15 demonstrated deficits in spatial learning and memory during acquisition as well as during a shifted platform phase where learning a new position was required. CONCLUSIONS: The results demonstrate that spatial learning and memory deficits produced by MA administration are dependent upon when the exposure of the animal occurs and appears to be during the period of development in the rat when the response to threatening environments, stressors, is greatly reduced.

Animals↗
PubMed2004

BetaCCM but not physostigmine enhancement of memory retrieval depends on emotional processes in mice.

RATIONALE: The effects of methyl beta-carboline-3-carboxylate (betaCCM, an inverse agonists of GABA/benzodiazepine receptors) or physostigmine (a cholinesterase inhibitor) on retrieval processes and relationships with anxiety have been only marginally studied. OBJECTIVE: This study investigates in mice the effects of acute betaCCM or physostigmine injections on retrieval of previously acquired discriminations involving distinct contextual cues (serial contextual discrimination; SCD) in a four-hole-board. Animals submitted to SCD were also evaluated for emotional reactivity in an elevated-plus maze. METHODS: Mice were injected before the learning session began with a saline solution. Twenty-four hours later, mice were replaced on the context of the initial acquisition and a single dose of saline or betaCCM (0.5 or 1.5 mg/kg) or physostigmine (0.05 and 1.0 mg/kg) was injected 20 min before testing. RESULTS: The highest dose of either betaCCM or physostigmine improved performance of the first discrimination in the SCD task. The higher dose of betaCCM produced anxiety-like reactivity in the plus maze, and scores of "anxiety" were significantly correlated with memory scores; in contrast, memory performance of physostigmine-treated subjects were totally independent of emotional reactivity. CONCLUSION: These results show that, as opposed to physostigmine, betaCCM acts on retrieval processes specifically through its emotional component.

Animals↗
PubMed1997

Effects of methylphenidate on spatial working memory and planning in healthy young adults.

Previous studies of the effects of the psychomotor stimulant, methylphenidate, have concentrated on vigilance and reaction time tasks. In this study, the effects of methylphenidate on more complex aspects of cognition were studied using tasks from the CANTAB battery and related tests which have been shown to be sensitive to frontal lobe dysfunction. Twenty-eight young healthy men participated in a counterbalanced, double-blind, placebo-controlled study of the effects of methylphenidate. Cognitive assessment included tests of spatial working memory, planning, verbal fluency, attentional set-shifting and sustained attention. Methylphenidate had significant effects on performance of the tests of spatial working memory and planning but not on the attentional and fluency tests. When the drug was taken on the first test session, performance on the spatial tests was enhanced by the drug compared to placebo. However, when the drug was taken second, performance accuracy was impaired whereas response latencies were decreased. These results are consistent with a hypothesis that methylphenidate influences performance in two conflicting ways; enhancing executive aspects of spatial function on novel tasks but impairing previously established performance. This pattern of effects is discussed within the framework of dual, interacting arousal mechanisms.

Adult↗
PubMed1998

N-methyl-D-aspartate receptors in the nucleus accumbens are involved in detection of spatial novelty in mice.

The aim of this study was to investigate the role played by intra-accumbens N-methyl-D-aspartate (NMDA) receptors in spatial information encoding. For this purpose, the effect of local administration of both competitive (AP-5) and non-competitive (MK-801) NMDA antagonists was assessed in a task designed to estimate the ability of rodents to encode spatial relationships between discrete stimuli. The task consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). The results show that both doses of MK-801 (0.15 and 0.3 microg/side) induced a selective impairment in the capability of mice to detect spatial novelty. A similar effect was obtained by injecting the low dose of the competitive antagonist AP-5 (0.1 microg/side), whereas the high dose (0.15 microg/side) abolished detection of both spatial and object novelty. Taken together, these results show that intra-accumbens injections of low doses of competitive and non-competitive NMDA antagonists can produce selective deficits in processing spatial information resembling those observed after hippocampal damage. Moreover, the fact that pharmacological treatments spare memory processes involved in habituation suggests that NMDA antagonists may interfere with the formation of spatial representations rather than producing memory deficits per se.

Animals↗
PubMed2001

Differential effects of delta 9-THC on spatial reference and working memory in mice.

RATIONALE: Marijuana remains the most widely used illicit drug in the U.S., and recent attention has been given to putative therapeutic uses of marijuana and cannabinoid derivatives. Thus, developing a better understanding of delta9-THC (tetrahydrocannabinol)-induced mnemonic deficits is of critical importance. OBJECTIVES: These experiments were conducted to determine whether delta9-THC has differential effects on spatial reference and working memory tasks, to investigate its receptor mechanism of action, and to compare these effects with those produced by two other compounds--scopolamine and phencyclidine--known to produce mnemonic deficits. In addition, the potency of delta9-THC in these memory tasks was compared with its potency in other pharmacological effects traditionally associated with cannabinoid activity. METHODS: Two different versions of the Morris water maze were employed: a working memory task and a reference memory task. Other effects of delta9-THC were assessed using standard tests of hypomotility, antinociception, catalepsy, and hypothermia. RESULTS: delta9-THC disrupted performance of the working memory task (3.0 mg/kg) at doses lower than those required to disrupt performance of the reference memory task (100 mg/kg), or elicit hypomotility, antinociception, catalepsy, and hypothermia. These performance deficits were reversed by SR 141716A. The effects of delta9-THC resembled those of scopolamine, which also selectively disrupted the working maze task. Conversely, phencyclidine disrupted both tasks only at a dose that also produced motor deficits. CONCLUSIONS: These data indicate that delta9-THC selectively impairs performance of a working memory task through a CB, receptor mechanism of action and that these memory disruptions are more sensitive than other pharmacological effects of delta9-THC.

Animals↗
PubMed2002

Percept-related changes in horizontal optokinetic nystagmus at different body orientations in space.

Large-field motion of the visual environment is a powerful stimulus to induce the perception of contra-directional self-motion in a stationary observer. We investigated the interrelations between horizontal optokinetic nystagmus and subjective states of motion perception under variation of subjects' orientation with respect to gravity. Subjects were tested sitting upright and lying supine, and signalled transitions between object- and self-motion perception whilst viewing an optokinetic stimulus rotating about the subjects' longitudinal axis at a range of angular velocities. Optokinetic stimulation in the supine condition resulted in subjects perceiving a graviceptive conflict and the illusory perception of whole body tilt in a direction opposite to optokinetic stimulus rotation, whereas during upright viewing the axis of stimulus rotation was aligned with the direction of gravity and thus did not result in a conflict or perception of tilt. In both postures, self-motion perception coincided with an increased deviation of mean horizontal gaze position in the perceived direction of heading with a concurrent reduction in optokinetic nystagmus slow-phase gain. Slow-phase gain was also significantly reduced in the supine position as well as at increasing stimulus velocities. The results demonstrate that spontaneous transitions between the perception of object-motion and that of self-motion consistently coincide with spatial attentional and orientational strategies, shifting from passive monitoring to active oculomotor exploration and anticipation.

Adult↗
PubMed2002

Conflicting sources of spatial information in a distance-reproduction task.

Previous research has shown that the reproduction of a criterion distance is biased towards previously coded endpoints. The purpose of this research was to illustrate that, in addition to the retention of endpoint information, the presence of conflicting sources of spatial information within a trial causes systematic response biases in distance reproduction. Three experiments were conducted in which participants performed rapid aiming movements on a digitising tablet that translated to movement of a cursor on a computer monitor. The required movement amplitude in all three experiments was 20 cm. In experiment 1, the location of the home and target positions on the monitor was fixed, but the initial position of the hand was varied randomly from trial to trial. In experiment 2, the change in position of the limb was matched by a corresponding change in the location of the monitor display. In experiment 3, the initial position of the limb was fixed, but the location of the display on the monitor varied from trial to trial. The results of experiments 1 and 2 showed that error varied as a function of the initial position of the limb. However, this effect was greater in experiment 1, where the mapping between the location of the monitor display and limb position varied from trial to trial. There was also an effect of varying the location of the monitor display in experiment 3, but this was smaller than varying initial limb position in experiment 1. These findings suggest that both the retrieval of previously specified endpoints and conflicts in the coding of spatial information contributed to the observed response biases in distance reproduction.

Adolescent↗
PubMed2002

Visuomotor transformations affect bimanual coupling.

Interactions between bimanual movements may occur at two different levels: at a visually based level, where movement trajectories are programmed within the visually perceived external space, and at the executional level, through crosstalk of sensorimotor signals arising during movement execution. In order to distinguish between these sources of interactions, we investigated bimanual reversal movements under different conditions of visual feedback. A visuomotor transformation dissociated movement execution from visual appearance on a computer screen. The transformation we used made movements of the same amplitude evoke different excursions, and made movements of different amplitudes entail matched excursions on the screen. The transformed conditions allowed us to study which parameters of bimanual coupling were related to the way movements were executed and which correlated with the visual movement display. We found a clear dissociation between execution-related and visually related bimanual interactions. The assimilation of movement amplitudes was completely execution-related. Whenever movements of different amplitudes were generated, the shorter movement was lengthened, irrespective of how the movements appeared on the feedback screen. In contrast, temporal coordination at the point of movement reversal, as well as trial-by-trial correlations of movement amplitudes, also showed significant effects of the visuomotor transformation, suggesting that these parameters are influenced by visually perceived effects of movements. This dissociation confirms the idea of separate pathways for bimanual interactions and shows that a specific set of bimanual interactions occur at least partly within a visually based external reference frame.

Acculturation↗
PubMed2003

Delay improves performance on a haptic spatial matching task.

Systematic deviations occur when blindfolded subjects set a test bar parallel to a reference bar in the horizontal plane using haptic information (Kappers and Koenderink 1999, Perception 28:781-795; Kappers 1999, Perception 28:1001-1012). These deviations are assumed to reflect the use of a combination of a biasing egocentric reference frame and an allocentric, more cognitive one (Kappers 2002, Acta Psychol 109:25-40). In two experiments, we have examined the effect of delay between the perception of a reference bar and the parallel setting of a test bar. In both experiments a 10-s delay improved performance. The improvement increased with a larger horizontal (left-right) distance between the bars. This improvement was interpreted as a shift from the egocentric towards the allocentric reference frame during the delay period.

Adolescent↗
PubMed2003

Aging effects on spatial tuning of hippocampal place cells in mice.

One reason the electrophysiological correlates of hippocampal neurons are of interest is the possibility that they reflect their representational properties, presumably spatial/relational ones. Stable spatial representations, based on activity of ensembles of hippocampal place cells, initially develop through a series of short-episodic spatial tunings. Hence these short-episodic spatial tunings are important for understanding the establishment of stable place fields. Studies of age-related changes in place cell activities traditionally focus on place fields. In the present study, we characterized the short-episodic spatial tunings (1-min bins) of hippocampal CA1 place cells of freely moving mice in a familiar cylinder arena, and compared these functions in young and old mice. Spatial tuning was expressed by spatial selectivity, which we found fluctuated across a 16-min recording session in both young and old mice. High spatial selectivity, which is mainly due to the low firing of a place cell out of the place field in young mice, was significantly higher in old mice. The high firing rate out of the place field was the main factor contributing to significantly lower spatial selectivity in old mice. In addition, young mice showed a broad peak in the spatial selectivity between 4 and 10 min. In contrast old mice showed no peak in the spatial selectivity during this time period. The stability of place fields after a 24-h interval was also lower in old mice than in young mice. The low spatial tuning and unstable place fields suggest that a hippocampal-based spatial representation was impaired in the old mice. Furthermore, we speculate that the age-related impairment in hippocampal inhibition system may be involved in the impaired spatial representation of hippocampal CA1 place cells in old mice.

Action Potentials↗