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At least 199 records · Page 11Linked to original sources
PubMed2001

Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation.

Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Effects of differential interference with postnatal cerebellar neurogenesis on motor performance, activity level, and maze learning of rats: a developmental study.

The region of the cerebellum was X-irradiated in infant rats with selected exposure schedules designed to produce animals in which the cerebellar cortex was (a) essentially normal except for agenesis of late forming granule cells with axons situated in the uppermost molecular layer (12--15X), (b) lacking in stellate cells, with a severe reduction in granule cells with axons in the upper molecular layer (8--15X), (c) morphologically disorganized but had only intermediate cell agenesis (4--5X), or (d) disorganized and devoid of practically all postnatally forming interneurons (4--15X). In the first two experiments young adults had to traverse rotating rods that differed in texture and types of obstacles. The 8--15X animals showed no deficits on any of the rods tested. The third study dealt with spontaneous motor performance in the open field at three ages. The 4--5X and 4--15X animals were hypoactive as infants and young adults; this was attributed to their motor deficits. The 8--15X and 12--15X animals were hyperactive in the open field as young adults. The fourth experiment examined intra- and/or intersession habituation. No group differences were found in habituation patterns. In the fifth experiment, using activity wheels, the 4--15X group was hypoactive, and the 8--15X and 12--15X groups were hyperactive as young adults. In the sixth experiment young adults were tested for learning performance in a multiple-unit water maze. The 4--15X group was deficient on single alternation; the 4--5X and 12--15X groups on double alternation. The seventh experiment shed some light on the single alternation deficit of the 4--15X group; only these animals failed to alternate spontaneously in a nonaversive situation. In conclusion, these behavioral results, combined with those of recent morphological investigations, suggest that the cerebellar cortex is hierarchically organized: The basal domain of Purkinje cells and the lower molecular layer are implicated in the coordination of movements; the apical domain of Purkinje cells and the upper molecular layer, in the coordination of actions.

Animals↗
PubMedDate not supplied

Age-related decline in water maze learning and memory in rats: strain differences.

Rats display an age-related impairment in learning and memory; however, few studies have systematically examined this relationship in multiple strains. The present study used a repeated acquisition water maze task to test the hypothesis that age-related decreases in learning and memory occur at different rates in three strains of rats, i.e. Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats. All three strains of rats displayed age-related decreases in spatial learning and memory; however, the rate of decline differed between the strains. Compared to young rats of the same strain, only SHR were significantly impaired at 12 months of age. All three strains displayed moderate impairment in learning the task at 18 months of age, and at 24 months of age all three strains of rats were severely impaired in the task, but SD performed best at 18 and 24 months of age. Further, SD and SHR displayed a probe trial bias at 3 months of age, but only SD had a bias at 12 months of age and none of the rats showed the bias at later ages. Thus, in these three strains, age-related impairment of spatial memory proceeds at different rates.

Aging↗
PubMed1993

Comparison of the short- and long-lasting effects of perforant path kindling on radial maze learning.

The present experiment compared the long-lasting with the short-lasting effects of kindling the perforant path input to the hippocampal formation on the acquisition of two radial maze tasks. Animals in the long-term group were fully kindled (i.e., Stage 5 motor seizures were evoked) prior to a stimulation-free training period. Animals in the short-term group were kindled 30-45 min prior to each learning trial. A third group of animals served as controls and were never kindled. On both 8-arm and 4/8-arm radical maze tasks, learning impairments were apparent only in the short-term group. Thus, the impaired learning is more likely related to the short-term aftereffects of an afterdischarge than to any long-term alterations in the neuronal status of the brain caused by kindling.

Animals↗
PubMed1994

Dissociation between conditioned taste aversion and radial maze learning following seizure-induced multifocal brain damage: quantitative tests of serial vs. parallel circuit models of memory.

Multivariate analyses between conditioned taste aversion (CTA) and radial maze acquisition (RMA) scores and percentages of neuronal dropout within thalamic and telencephalic structures were completed for rats in which overt seizures had been evoked following a single systemic injection of lithium/pilocarpine. Despite multifocal damage, only the amount of damage within the hippocampus (CA1) and the basolateral amygdala was most strongly associated with attenuated CTA, whereas damage within the mediodorsal thalamus was primarily associated with RMA. There was no significant correlation between CTA or RMA. Multiple regression analyses for specific Paxinos and Watson structures and their traditional aggregates supported more precise delineation of neuronal substrates of learning/memory and a multimodal (parallel) model for these processes.

Animals↗
PubMed2006

Impairments in water maze learning of aged rats that received dextromethorphan repeatedly during adolescent period.

RATIONALE: Dextromethorphan (DM), an over-the-counter cough suppressant, has been recently used as a drug of abuse by teenage groups in some countries, such as the United States, Canada, and Korea. We previously showed that repeated administration of DM, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, impairs spatial learning performance in adolescent rats. OBJECTIVES: In the present study, long-term adverse effects of repetitive DM use at adolescence were examined in rats. METHODS: Male and female Sprague-Dawley rat pups received either intraperitoneal DM (40 mg/kg) or saline daily during postnatal days 28-37, and were then subjected to the Morris water maze task at the age of 18 months. Expression levels of NMDAR1, functional subunit of NMDA receptors, in the prefrontal cortex and the hippocampus were examined by Western blot analysis. Changes in plasma corticosterone levels responding to stress were determined by radioimmunoassay. RESULTS: DM-experienced male rats exhibited deficits in the probe trial, and female rats in the initial learning and the reversal training, in water maze performance. Expression levels of NMDAR1 in the brain regions were significantly increased in DM-experienced rats, compared to control rats. Stress-induced increases in plasma corticosterone levels were blunted both in male and female DM rats. CONCLUSIONS: The results suggest that repeated administration of DM at high doses during adolescent period may induce permanent deficits in cognitive function and that increased expression of NMDAR1 in the prefrontal cortex and the hippocampus may take a role in DM-induced memory deficits.

Animals↗
PubMed2001

Involvement of dopamine D(2) receptors in complex maze learning and acetylcholine release in ventral hippocampus of rats.

In the current study we focus on the involvement of dopamine D(2) receptors in the ventral hippocampus in memory performance and acetylcholine release. Using the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride, a D(2) receptor antagonist, into the ventral hippocampus (8 microg/kg) was found to impair memory performance. Co-injection of quinpirole, a D(2) receptor agonist (8 microg/kg), overcame the impairment in performance. Microdialysis study revealed that quinpirole infusion (10-500 microM) into the ventral hippocampus stimulated acetylcholine release in a dose-dependent manner, and systemic injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release in the ventral hippocampus. Infusion of eticlopride, another D(2) receptor antagonist, into the ventral hippocampus suppressed acetylcholine release in the hippocampus induced by systemic injection of quinpirole. Taken together, we suggest that D(2) receptors in the ventral hippocampus are involved in memory performance, possibly through the regulation of acetylcholine.

Acetylcholine↗
PubMed1991

Maze learning in Alzheimer's disease.

Alzheimer's disease (AD) patients and normal elderly controls performed a block of 10 trials on a finger maze, followed by a 45-min period during which verbal learning measures were administered. Subjects then performed an additional 10 trials on the original maze, followed by 10 trials on a new maze. The AD patients and a subset of control subjects decreased mean completion time across Blocks 1 and 2, suggesting skill acquisition. Mean time on Block 3 was significantly less than mean time on Block 1, suggesting skill generalization. A subset of controls did not show the above pattern. The results of this study suggest that AD patients are able to acquire and generalize a cognitively mediated perceptual-motor skill.

Aged↗
PubMed1996

Acute and chronic arecoline: effects on a scopolamine-induced deficit in complex maze learning.

These studies tested the effect of arecoline, a nonselective muscarinic agonist, administered either acutely or by chronic peripheral infusion via osmotic minipumps, on a scopolamine-induced deficit in a Stone (14 unit) T-maze task in rats. Scopolamine alone (0.125-1.0 mg/kg, IP) dose-dependently impaired maze acquisition, increasing maze run-times and to a lesser extent, the number of errors committed. Neither acute administration of arecoline (5.0 and 10.0 mg/kg, IP), when tested against a deficit induced by scopolamine (0.25 mg/kg, IP), nor chronic arecoline administration (30 and 50 mg/kg per 24 h), when tested against a deficit induced by scopolamine (0.5 mg/kg), were able to ameliorate the decrements in maze performance. In fact, the higher dose of arecoline (50 mg/kg per 24 h) infused over 10 days potentiated the scopolamine-induced deficit, with respect to latency. These data indicate that dose selection is of great importance when employing arecoline in tests of learning and memory and that the influence of the method of administration of arecoline on the behavioural outcome warrants further study.

Animals↗
PubMed2001

Ameliorative effects of azaindolizinone derivative ZSET845 on scopolamine-induced deficits in passive avoidance and radial-arm maze learning in the rat.

Effects of ZSET845 (3,3-dibenzylimidazo[1,2-a]pyridin-2-(3H)-one), a newly synthesized cognitive enhancer, and donepezil and tacrine on the scopolamine-induced cognitive deficits in rats were examined in passive avoidance and radial-arm maze tasks. ZSET845 (0.01 mg/kg) showed a greater ameliorative effect than donepezil (0.1 mg/kg) or tacrine (1 mg/kg) in the passive avoidance task. In the radial-arm maze task, ZSET845 (0.1 mg/kg) also showed a greater effect than donepezil (10 mg/kg) or tacrine (10 mg/kg). ZSET845 induced an increase in the choline acetyltransferase (ChAT) activity in the hippocampus, suggesting that the ameliorative effects of ZSET845 are related to the increase in the ChAT activity in the hippocampus.

Alzheimer Disease↗
PubMed1998

Improved maze learning through early music exposure in rats.

Rats were exposed in utero plus 60 days post-partum to either complex music (Mozart Sonata (k. 448)), minimalist music (a Philip Glass composition), white noise or silence, and were then tested for five days, three trials per day, in a multiple T-maze. By Day 3, the rats exposed to the Mozart work completed the maze more rapidly and with fewer errors than the rats assigned to the other groups. The difference increased in magnitude through Day 5. This suggests that repeated exposure to complex music induces improved spatial-temporal learning in rats, resembling results found in humans. Taken together with studies of enrichment-induced neural plasticity, these results suggest a similar neurophysiological mechanism for the effects of music on spatial learning in rats and humans.

Analysis of Variance↗
PubMed2002

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice.

Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.).

Affect↗
PubMed1996

Infusion of (+) -MK-801 and memantine -- contrasting effects on radial maze learning in rats with entorhinal cortex lesion.

(+)-5-Methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate ((+)-MK-801) and 1-amino-3,5-dimethyladamantane (memantine), two uncompetitive antagonists of the NMDA receptor were tested in an allocentric version of the radial maze test (with four out of eight arms reinforced) both in normal rats and after quinolinic acid-induced entorhinal cortex lesions. Both agents were infused s.c. using Alzet osmotic minipumps in order to assure steady state drug levels in the serum and brain during the experiment. In non-lesioned rats, (+)-MK-801 (0.312 mg/kg per day) produced disturbances in learning of spatial information dependent on reference memory but not that involving working memory. In contrast, memantine (20 mg/kg per day) had no effect in normal rats. In rats with entorhinal cortex lesions, (+)-MK-801 enhanced the lesion-induced deficit in reference memory. In contrast, memantine reversed the lesion-induced increase in reference memory errors. The divergent effects of those two uncompetitive NMDA receptor antagonists could, at least partially, be due to the differences reported in their channel blocking kinetics and voltage dependence. The results indicate that under conditions of pathological impairment of brain structures such as entorhinal cortex lesion, memantine might produce beneficial effects on cognitive functions.

Animals↗
PubMed2006

Hippocampal synaptic plasticity and water maze learning in cocaine self-administered rats.

Previously, we have shown that long-term potentiation (LTP) in hippocampus of Lewis rats was significantly modulated by cocaine self-administration. Using a single train of high-frequency stimulation of 100 Hz for 1s (HFS), we found an enhancement of LTP after cocaine self-administration that was maintained even during the extinction of this behavior. However, the effects of cocaine self-administration on a hippocampal-dependent spatial learning task were unknown. Therefore, in the present study our first objective was to analyze if cocaine self-administration might affect the performance in a hippocampus-dependent task, such as the Morris water maze test. Male adult Lewis (LEW) rats self-administered cocaine (1 mg/kg/injection) or saline (0.9% NaCl) for 3 weeks. Three hours after finishing the last self-administration session, animals were submitted to Morris water maze training for 3 consecutives days. A memory test was carried out 24 h after the last training session. No significant differences were found in escape latencies and time spent in the quadrant where the platform was located during training. Given that we did not find any cocaine effect on this spatial learning task, our second objective was to estimate indirectly if brain cocaine levels have failed to modulate LTP in animals that were performing the water maze trials. To this end, we tested if cocaine application to hippocampal slices of naïve subjects was able to evoke LTP. The results indicated that cocaine produced an enhanced LTP in these hippocampal slices. Taking together, the results of the present study suggest that hippocampal LTP-like processes generated after cocaine self-administration are not related to spatial learning hippocampal-dependent tasks, such as the water maze test.

Animals↗
PubMed2001

Effects of amyloid-beta-(25-35) on passive avoidance, radial-arm maze learning and choline acetyltransferase activity in the rat.

To investigate the neurotoxicity of amyloid-beta-(25-35), which is thought to be the active site of amyloid-beta, the peptide was injected into the lateral ventricle of rats. A single intracerebroventricular (i.c.v.) injection of amyloid-beta-(25-35) at a dose of 15 nmol/rat induced a marked decrease in latency in step-through passive avoidance task. Amyloid-beta-(35-25), reverse sequence of amyloid-beta-(25-35), was without harmful effects on passive avoidance performance. The amyloid-beta-(25-35) at a dose of 5 or 15 nmol/rat impaired radial-arm maze performance, and induced a decrease in choline acetyltransferase activity in the medial septum, cortex and hippocampus, but not in the basal forebrain. The number of choline acetyltransferase-immunoreactive cells in the medial septum was decreased, in conformity with the decrease in choline acetyltransferase activity of the area. These results suggest that learning and cognitive disturbance induced by i.c.v. injection of amyloid-beta-(25-35) is associated with the dysfunction of cholinergic neuronal system in the brain.

Amyloid beta-Peptides↗
PubMed1993

The effects of ethanol exposure on radial arm maze learning and behavior of offspring rats.

The effects of maternal drinking on offspring have been studied epidemiologically, in human beings, and experimentally, in rats. The physical growth of offspring of female alcoholic rats, including histological growth of brain, lung, thymus gland, liver, and kidney, was previously reported by us. In the present study, we observed the effect of ethanol intake by the mother rat on learning ability and behavior of offspring rats using an eight radical arm maze. At the same time histological observations of the cerebrum were carried out. The mother rat was exposed to ethanol from a young age to delivery (P-DEL) or to weaning (P-NURS). After weaning, the offspring was exposed to ethanol until the tests began (P-WEAN). Experimental groups, classified by length of ethanol exposure, as mentioned above, disclosed the following: (1) Number of trials required for fulfilling learning criterion was significantly large in P-DEL and P-NURS rat groups relative to the controls; that is, P-DEL and P-NURS rats were slow in learning. (2) Numbers of rats which did not fulfill the learning criterion were: Group P-DEL, one male of eight; Group P-NURS, three males of seven. The behavior of the rats in Group P-WEAN differed from those in other groups; while they were receiving acclimation training, they were, unlike ordinary rats, not watchful of the device, slow to find the feed, and indifferent. They seemed to lack carefulness and sometimes failed to eat the feed even though they succeeded in selecting correct arms. Their motion was abrupt and they ran at extraordinarily high speeds. (3) In the observations of correct choices in the first eight choices, groups P-DEL and P-NURS showed significantly low values. This suggested the lowering of their learning ability. (4) In the observations of continuous correct choices, Group P-DEL showed a significantly low value. This suggested the rats did not learn thoroughly enough to retain their acquisition long. (5) Body weight, learning ability, and hippocampal neurons were affected by ethanol exposure more severely in Group P-NURS than in Group P-DEL. An even more severe effect was observed in Group P-WEAN.

Animals↗
PubMed1980

[Studies on the development of water maze-learning ability in rats. (1) Correlation between learning ability and brain weight in growth periods (author's transl].

In order to determine the appropriate age for the water filled multiple T-maze test. Wistar-Imamichi strain rats (SPF) 3 to 10 weeks of age were given daily 3 repeat trials on three consecutive days. Learning ability was evaluated on the basis of daily decrease of errors in the water maze test. Elapsed time to reach the goal, errors and variations of these decreased with progressing trials regardless of age and sex. Comparing to the rats under 4 weeks of age, errors in the 3rd day trials became constant at lower level in rats over 5 weeks of age. These results suggest that the learning ability of rat may reach adulthood by 5 weeks of age. Brain weight also attained a plateau at 4-5 weeks of age in both sexes of rats.

Age Factors↗