Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact

This experiment utilized a laterally placed controlled cortical impact model of traumatic brain injury (TBI) to assess changes on spatial learning and memory in the Morris water maze (MWM). Adult rats were subjected to one of two different levels of cortical injury, mild (1 mm) or moderate (2 mm) deformation, and subsequently tested for their ability to learn (acquisition) or remember (retention) a spatial task, 7 or 14 days after injury. Results revealed an injury-dependent deficit for experimental animals compared to sham-operated controls. Not only did the TBI result in longer escape latencies, but also significant deficits in search time and relative target visits. Although the moderately injured animals demonstrated significant histopathology in the cortex and hippocampus, mildly injured subjects demonstrated no obvious tissue destruction, but did manifest significant behavioral change. These results demonstrate that a laterally placed controlled cortical impact is capable of producing significant cognitive deficits on both acquisition and retention paradigms utilizing the MWM.     

Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task.

This study examined the effect of hippocampal lesions on acquisition of the Morris water maze and conditioned-fear task in inbred mice. C57BL/6J, DBA/2J, and B6D2F1 hybrid mice were given hippocampal lesions or sham surgery and then tested. The lesioned C57BL/6J and B6D2F1 mice failed to learn the Morris task relative to sham-operated controls, and no DBA group learned the task. In the contextual component of conditioned fear, lesions decreased freezing in all strains. But the lesions only affected freezing to the conditioned stimulus in the DBA/2J and B6D2F1 strains. These data demonstrate that C57BL/6J and B6D2F1 mice use the hippocampus to solve the Morris water maze and conditioned-fear task, and the DBA mice use the hippocampus, to some degree, in the conditioned-fear task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nitric oxide is involved in the formation of learning and memory in rats: studies using passive avoidance response and Morris water maze task

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml).     

Differential effect of ketamine on the reference and working memory versions of the Morris water maze task.

The assumption that blockade of long-term potentiation by N-methyl-D-aspartate antagonists interferes with spatial memory was supported by experiments showing that 15 mg/kg ketamine impairs acquisition of navigation to a hidden platform but not to a visible platform. Higher doses were required to impair retrieval of overtrained place navigation. In a working memory version of the task, retrieval latencies were shorter than acquisition latencies with 4- to 15-min but not with 30- and 60-min delays. Latent learning was only effective with the 4-min delay. Ketamine prolonged the initial search of the hidden platform at 3 mg/kg and impaired latent learning but not active acquisition at 1.5–20 mg/kg. Comparison of behavioral and synaptic effects of ketamine suggests that long-term potentiation is a necessary condition, but not a sufficient condition, for acquisition of place navigation, because search strategy and latent place learning are impaired by ketamine doses not interfering with this synaptic phenomenon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation of spatial learning of rats in the Morris water maze task to the number of viable CA1 neurons following four-vessel occlusion.

Male Wistar rats were tested in the Morris water maze task 1 wk after 6, 9, or 12 min of transient global ischemia. The 9-min and 12-min ischemia groups were significantly impaired in the acquisition and the reversal experiment. A systematic counting of CA1 neurons in the whole hippocampal formation revealed a unilateral number of CA1 neurons of 286,000 in the sham group, of which two-thirds were located in the dorsal hippocampus. The ischemia groups showed a significant decline in the number of dorsal CA1 neurons, whereas only the 12-min ischemia group showed a significant but minor decline (10–25%) in the number of ventral CA1 neurons. A correlation analysis showed that the escape distance declined with increasing number of viable CA1 neurons, but poor correlation coefficients were obtained. Thus, some of the ischemic rats with even very few viable CA1 neurons in the dorsal hippocampus were capable of performing this spatial learning task at sham-group level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability, distribution, and validity of age-related cognitive deficits in the Morris water maze

In the present study, F-344 rats throughout 1.5 to 26 months of age were tested in the reference memory version, a moving-platform repeated acquisition version, and in a cued platform version of the Morris water maze. The results suggest that: (1) performance in the water maze declines continuously, beginning at the earliest age, and very closely fits a linear function; (2) there are robust, reliable differences between individuals in terms of their performance in the Morris water maze, but chronological age accounts for only a fraction of the variance between individuals; (3) there is no evidence of a bimodal distribution among aged rats--there is no distinct subgroup of individuals that performs so poorly that they are qualitatively different from the majority of the population, and distinctions between "impaired" and "unimpaired" subjects must be based on arbitrary criteria that may not be consistent from one study to the next; (4) age-related deficits in the Morris water maze may not be restricted to learning and memory, but may also include deficits in attention, the ability to process spatial information, and/or the ability to develop efficient spatial search strategies; and (5) swim distance is the most appropriate measure of cognitive function in the Morris water maze, but the relationship between this measure and other measures of noncognitive function make it clear that swim distance may not be a pure measure of cognitive function. Although the Morris water maze remains a valuable preclinical test with better validity and specificity than many other behavioral tests, measures of performance in the Morris water maze should not be considered synonymous with cognitive function.     

Posttraining paradoxical sleep in rats is increased after spatial learning in the Morris water maze.

The role of posttraining paradoxical sleep (PS) in spatial or nonspatial learning in the Morris water maze was evaluated. Sprague-Dawley rats were given a 12-trial training session in either the hidden or the visible platform versions of the task. Subgroups then underwent paradoxical sleep deprivation (PSD) beginning at different times after training. Rats with PSD imposed from 14 hr after spatial training had poorer retest scores than any other group. Other rats, implanted with electrodes to permit continuous recording of sleep electroencephalography, were found to undergo a prolonged period of elevated PS after spatial training. By contrast, rats trained in the nonspatial version of the water maze task did not show retention deficits after PSD or elevated PS after training. These results support a role for PS in spatial, but not nonspatial, learning in the Morris water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics

A group of novel neuroleptics (e.g. olanzapine, seroquel, sertindole and ziprasidone) and already marketed compounds (e.g. clozapine, haloperidol and risperidone) were tested for acute effect on spatial learning and memory in Morris' water maze task. Young rats were trained for 4 consecutive days (three trials/day) to find a platform situated beneath the water surface. Two compounds, sertindole and seroquel, were without effect on spatial performance, whereas clozapine impaired performance on the first 2 test days but showed no effect compared to the controls on the last 2 test days. Ziprasidone and olanzapine markedly impaired spatial memory without affecting motor function (measured by the swimming speed). Risperidone and haloperidol also impaired performance but in addition both compounds significantly lowered the swimming speed. The present study indicates that several of the compounds impair spatial learning in Morris water maze. This might be of clinical importance in the treatment of schizophrenics, as many of these patients already show severe cognitive deficits. Therefore, certain antipsychotics could worsen the preexisting memory deficits in schizophrenic patients and this aspect should be considered before antipsychotic treatment.     

Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial water maze.

Tested the disruptive effect of cholinergic blockade under conditions in which either the working memory or the spatial mapping requirements of the behavioral task were emphasized. In Exp I, 13 male hooded rats were trained in an 8-arm radial water maze to asymptotic performance. When delays of 5, 10, 20, and 40 min were inserted between Choice 4 and Choice 5, incidence of errors in Choices 5–8 increased after pretrial (20 min) intraperitoneal scopolamine (0.2 mg/kg) faster than under control conditions and approached chance level with the 40-min delay. Scopolamine after Choice 4 or pretrial methylscopolamine was ineffective. In Exp II, 30 Ss were trained in a Morris water tank. Acquisition was impaired by pretrial injection (20 min) of 0.1 and 0.2 mg/kg scopolamine, but a higher dose (1.0 mg/kg) was required to impair overtrained performance. In a working memory version of the navigation task, scopolamine administered 20 min before the 1st trial deteriorated retention tested 40 min later at a dose of 1.0 but not at 0.4 and 0.2 mg/kg. It is concluded that the disruptive effect of scopolamine is proportional to the demands on the working memory component of the task, whereas the use of an overtrained mapping strategy is relatively resistant to cholinergic blockade. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal–perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 sec or 5 min) imposed between each sample trial and retention test. Entorhinal–perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 sec. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relative influence of place and direction in the Morris water task.

Previous work from our laboratory has demonstrated that rats display a preference for directional responding over true place navigation in the Morris water task. The present study evaluated the range of situations in which this preference is observed and attempted to identify methods that favor navigation to the precise location of the escape platform in the room. A preference for directional responding over place navigation was observed in a wide range of procedures that included providing extensive training (Experiment 1), providing only platform placement experience in the absence of active swim training (Experiment 2), training navigation to multiple platform locations in a moving platform variant of the task (Experiment 3), and explicitly training navigation to a precise location in the room, versus navigation in a particular direction, regardless of the pool's position in the room (Experiments 4-5). A modest preference for navigation to the precise spatial location of the platform was observed when the pool wall was virtually eliminated as a source of control by filling it to the top with water (Experiment 6). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A two-platform task reveals a deficit in the ability of rats to return to the start location in the water maze.

The ability of rats to return to the start location was examined with a 4-arm radial water maze. The task required rats to find 2 hidden platforms in sequence. Rats were released from 1 of 3 arms and there was a platform located in the fourth arm. Once a rat found this platform, a 2nd platform was raised in another location, which was either the start location, for 1 group, or another fixed location, for a control group. Across 3 experiments, all rats learned the location of the 1st fixed platform in 80 to 120 trials. However, rats had difficulty finding a 2nd platform if it was at the start location. Control groups revealed that rats could learn 2 platform locations and that the difficulty in learning to return to the start location did not seem to be attributable to its aversive nature. In separate groups, exposure to the start location was increased by starting the rats from an initially stable platform. Rats still did not readily learn to return to the start location. The authors suggest that start location, when varied, cannot readily be used to define the location of a hidden platform. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging and atropine effects on spatial navigation in the Morris water task.

A recent animal model that has been particularly useful in the neurobiology of aging has been the age-related decline of spatial information processing capacity in Sprague-Dawley rats measured in the place-learning water task developed by Morris (1981). In the first experiment of the present study, place behavior was examined in young (6 months), old (23–24 months), and very old (28 months) rats of another strain, Long-Evans. As an analogue of aging-related cholinergic dysfunction the effects of atropine sulfate (5–50 mg/kg), an anticholinergic drug that is known to disrupt behavior in this task, also was determined. Place navigation was not impaired in undrugged rats, even those in the oldest age group. Rats treated with atropine showed dose-dependent deficits. In a second experiment, young (4–5 months), old (18–20 months), and very old (28 months) Fischer-344 rats were examined. Place navigation was impaired in the old rats. The very old (28 months) rats could not swim well enough to be tested adequately. Although nonspatial deficits associated with aging may be found across most strains tested, there appear to be very large strain-related differences in spatial processing ability as a function of age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial localization in the Morris water maze in rats: Acquisition is affected by intra-accumbens injections of the dopaminergic antagonist haloperidol.

Previous studies (e.g., G. E. Ploeger et al; see record 1993-20962-001) showed that low doses of systemically injected haloperidol affected spatial learning in the Morris water maze. This study investigated effects of intra-accumbens injections of haloperidol on spatial learning. To control for motivation and sensorimotor coordination, the researchers trained rats to escape onto a visible platform. Low doses (50–200 ng) of haloperidol impaired spatial learning, whereas escaping on a visible platform was undisturbed. The 500-ng dose of haloperidol completely blocked acquisition because of combined learning and motor impairments. Retrieval of an acquired escape response was unaffected by 500 ng haloperidol. The data show that mesolimbic dopaminergic activity is involved in the acquisition of spatial localization. The results are related to studies demonstrating the involvement of the nucleus accumbens in cue-directed behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.     

Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training.

Sex differences in rats' performance on a stationary hidden-platform task (spatial task) in the Morris water maze and the effects of initial nonstationary hidden platform training (NSP training) were examined. The NSP training was designed to familiarize rats with the general requirements of the water-maze task without providing spatial information. NSP training led to faster acquisition and improved retention of the subsequent spatial task in both males and females. There was a sex difference favoring males on acquisition and retention of the spatial task only in rats that had not received previous NSP training. Moreover, there was an apparent reversed sex difference favoring females on some measures of spatial performance in NSP-trained rats. These results suggest that performance on the water-maze task, including the expression of sex differences, can be altered by previous familiarization with nonspatial aspects of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vasopressin fragment, AVP-(4-8), improves long-term and short-term memory in the hole board search task

To investigate the neurotoxicity of acetaldehyde covalent adducts, immunohistochemical staining for acetaldehyde adducts using the antibody against acetaldehyde adducts, was performed in the cerebral cortex of ethanol-fed (withdrawal) mice. In the ethanol-fed mice, the degeneration in the cerebral cortex was found, while the protein epitope related to acetaldehyde was found in the cerebral cortex, liver and adrenal cortex. No histochemical and immunohistochemical changes in the tissues from the control mice were found. It is possible that acetaldehyde adducts may effect on the cerebral cortex as the neurotoxicity which cause psychosis such as delirium and hallucination after alcohol drinking.     

Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze.

The Morris water maze task was originally designed to assess the rat's ability to learn to navigate to a specific location in a relatively large spatial environment. This article describes new measures that provide information about the spatial distribution of the rat's search during both training and probe trial performance. The basic new measure optimizes the use of computer tracking to identify the rat's position with respect to the target location. This proximity measure was found to be highly sensitive to age-related impairment in an assessment of young and aged male Long-Evans rats. Also described is the development of a learning index that provides a continuous, graded measure of the severity of age-related impairment in the task. An index of this type should be useful in correlational analyses with other neurobiological or behavioral measures for the study of individual differences in functional/biological decline in aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: Relationship to performance on the Morris water maze.

Tested young and aged Fischer 344 rats on the place and cue versions of the Morris water maze task. Although all of the young animals reached criterion within the 8-day testing period, the aged animals could be divided into 2 groups on the basis of their performance to criterion: achievers and nonachievers. Upon completion of the water maze testing, the animals were sacrificed, and their brains were processed for in vitro autoradiography of hippocampal excitatory amino acid receptors. Significant differences were found between the young and old rats in the levels of N-methyl-{d}-aspartate, CPP, kainate, and AMPA binding in subregions of the hippocampus. Despite the age-related decline in hippocampal glutamate receptors, no relationship was observed between the density or distribution of excitatory amino acid receptors and performance on the water maze task in the aged rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)