Radial-arm Maze Learning Research Articles

Sex differences in vicarious trial-and-error behavior during radial arm maze learning

We investigated sex differences in VTE behavior in rats during radial arm maze learning. Females made more VTEs than males, although there were no sex differences in learning. Further, VTEs and errors were positively correlated during the latter testing sessions in females, but not in males. This sex difference may be a reflection of differences between the sexes in conflict behavior or cognitive strategy while solving the maze.

Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period

Newborn mice were administered Fe 2+ (iron succinate: 7.5 mg/kg, b.wt) on either Days 3–5, 10–12 or 19–21, or vehicle (saline) at the same times, postnatally. Spontaneous motor behaviour and radial arm maze learning were tested at the age of 3 months. It was found that mice treated with Fe 2+ during postnatal Days 10–12 were markedly hypokinetic during the 1st 20-min test period and hyperkinetic during the 3rd and final 20-min test period. These mice showed an almost complete lack of habituation of spontaneous motor activity parameters to the test chambers. In the radial arm maze, the Days 10–12 treatment group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets; these mice showed also a severe trial-to-trial retention deficit as indexed by retention quotients. These behavioural deficits were observed also in animals treated with Fe 2+ during postnatal Days 3–5, but the effects were less pronounced, indicating the higher susceptibility of the brain for Fe 2+-induced damage during Days 10–12 postpartum. Treatment with Fe 2+ on Days 19–21 did not induce behavioural alterations in comparison with its respective control (vehicle) group. Analysis of total brain iron content indicated significantly more iron (μg/g) accumulation in the basal ganglia, but not frontal cortex, of mice from the Days 3–5 and 10–12 Fe 2+ (7.5 mg/kg) treatment groups. The contribution of iron overload during the immediate postnatal to later functional deficits seems to implicate symptoms of Parkinsonism but the kinetics of iron uptake to the brain and its regional distribution at this critical period of development awaits elucidation.

Neonatal Iron Exposure Induces Neurobehavioural Dysfunctions in Adult Mice

Excess iron in the brain has been implicated in the pathogenesis of several human neurodegenerative disorders, i.e., Parkinson's and Alzheimer's disease. The neonatal period is critical for the establishment of normal iron content in the adult brain. In the present study, the long-term neurobehavioral effects of iron exposure during this period were assessed by treating NMRI mice orally with 0.0, 3.7, or 37.0 mg Fe2+/kg body wt on postnatal days 10–12. Spontaneous motor behavior and radial arm maze learning were tested at the age of 3 months. It was found that the mice treated with the higher dose of Fe2+, 37.0 mg/kg body wt, were hypoactive during the first 20 min of testing but hyperactive during the final 20 min, showing an almost complete lack of habituation of spontaneous activity in the test chambers. These changes were also seen in animals treated with the lower dose of Fe2+, 3.7 mg/kg body wt, but the effects were less pronounced, indicating a dose–response relationship. In the radial arm maze, the Fe2+ 37.0 mg/kg group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets. Both dose groups showed attenuated performance increments on successive trials. Analysis of brain iron content indicated significantly more total iron (μg/g) in the basal ganglia, but not frontal cortex, of the higher, 37 mg/kg, dose group. The knowledge of the long-term effects of iron entering the brain during this critical period of rapid brain growth is limited. Increased amounts of iron in the brain, especially in the basal ganglia, may contribute to neurodegenerative processes.

Pfiesteria Toxin and Learning Performance

Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague–Dawley rats were injected (SC) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels. Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies. Published by Elsevier Science Inc.

Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat

FRITTS, M. E., E. T. ASBURY, J. E. HORTON AND W. L. ISAAC. Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat. PHYSIOL BEHAV 64(3) 373–380, 1998.—The rat medial prefrontal cortex (PFC) is believed to play a central role in working memory and selective attention processes. More recently, it has been shown that the effects of large PFC lesions on working memory may be due to the prelimbic area of the PFC. The aim of the present study was to compare the effects of lesions of the prelimbic area with PFC lesions that involved or spared the prelimbic area on shuttlebox avoidance and radial maze learning in rats. The findings indicate that rats with PFC lesions that spared the prelimbic area were impaired at avoidance but not radial arm maze learning, whereas rats with prelimbic lesions or PFC lesions that included this area were impaired on the radial arm maze but not the avoidance learning task. Results support the notion that the medial frontal cortex of the rat is a functionally dissociable region and suggest that the prelimbic area appears to be critical for working memory, but less so for attention processes.

Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice

Age-related changes in spatial learning performance were studied in relation to acetylcholine (ACh) content of brain regions in male aged (28-month-old) and young (5-month-old) mice of BDF1 strain. As there were large individual differences in the spatial performance of aged mice, the aged mice were divided into two subgroups, old A and old B. The old A group included the six best performers out of the 12 aged mice and the old B group included the remaining 6 worst performers. In a radial-arm maze task with 8 baited arms, aged mice in the old B group showed a marked deficit in acquisition performance and habituation to the apparatus. In the more difficult maze task with only 4 baited arms, the aged mice in the old B group exhibited marked impairment both in working memory and reference memory throughout training, whereas the aged mice in the old A group showed deficits in reference memory during the first 20 days of training and working memory during the last 20 days relative to young mice. Neurochemical analysis revealed significant decreases in the ACh content of the hippocampus and striatum in both aged groups, and in the frontal cortex and posterior cortex of the old B group as compared to the young group. Correlational analysis showed significant correlations between learning performance in the spatial task and ACh levels in the hippocampus, frontal cortex, and posterior cortex. The present results demonstrate that a marked decrease in ACh levels in the hippocampus and cerebral cortex may be closely related to behavioral impairment in spatial learning and habituation in fully aged mice. Thus, this particular strain of mice may serve as a useful animal model for age-related impairment of cognitive functions in relation to hypofunction of the cholinergic systems in the basal forebrain.

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). Alter 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: (I) 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.

Learning behaviour in chronic vitamin E-deficient and-supplemented rats: radial arm maze learning and passive avoidance response

The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.

Age-related changes in radial-arm maze learning and basal forebrain cholinergic systems in senescence accelerated mice (SAM)

Age-related changes in learning performance and the brain cholinergic system were studied in a senescence accelerated mice-prone series (SAM-P/8) and a senescence accelerated mice-resistant series (SAM-R/1, control) bred under specific pathogen-free conditions. In a radial-arm maze task, SAM-P/8 mice at 4 and 12 months of age showed virtually no significant impairment in working memory or reference memory compared with SAM-R/1 mice at the same age, although they needed more time to complete a trial than SAM-R/1. In contrast, in a passive avoidance task, SAM-P/8 showed a marked age-accelerated deficit in acquisition performance relative to SAM-R/1. Also, SAM-P/8 showed an age-accelerated decrease in locomotion and rearing in an open-field box. At the end of these behavioral tasks, neurochemical analyses showed that there were no differences in the concentrations of acetylcholine (ACh) in the cortex, hippocampus, striatum, midbrain, or cerebellum between SAM-P/8 and SAM-R/1. Although SAM-P/8 mice did not demonstrate any age-accelerated decline in radial-arm maze performance, they showed a normal age-related decline particularly in working memory, equal to that observed in SAM-R/1. Also, ACh levels in the aged groups of SAM-P/8 showed a significant decrease related to normal aging in the hippocampus and striatum, and a slight decrease in the cortex compared to the young group of the same strain. Thus, we found that SAM-P/8 show dissociative effects of aging in spatial learning and passive avoidance performance.

Transplantation of ventral forebrain cholinergic neurons to the hippocampus ameliorates impairment of radial-arm maze learning in rats with AF64A treatment

Two types of cholinergic neurons were transplanted into the hippoccampus of adult rats chemically damaged by lateral ventricular administration of AF64A, a cholinergic neurotoxin, and the effects were compared with respect to their ability to reinnervate the hippocampus and to repair behavioral deficit. Pieces of brain tissue containing the nucleus basalis magnocellularis (NBM) or the striatum were taken for grafting from 17-day rat fetuses. About 3 months after transplantation, the rats with bilateral NBM grafts showed significant amelioration in radial-arm maze performance and habituation to a novel environment in an open field box, although they had not recovered to the control level. In rats with NBM grafts that showed a good performance, there were surviving grafts and many ingrowths of AChE-positive fibers in the hippocampus. By contrast, rats with striatal grafts showed hardly any significant improvement in these behavioral measures. The AChE staining revealed poor outgrowth of the striatal grafts into the hippocampus. These results indicate that grafting of NBM cholinergic neurons, which are anatomically similar to septal neurons, into the hippocampus produces a partial restorative effect on the cognitive impairment associated with hypofunction of the septohippocampal system.

Transplantation of ventral forebrain cholinergic neurons to the hippocampus ameliorates impairment of radial-arm maze learning in rats with AF64A treatment

Abstract Two types of cholinergic neurons were transplanted into the hippocampus of adult rats chemically damaged by lateral ventricular administration of AF64A, a cholinergic neurotoxin, and the effects were compared with respect to their ability to reinnervate the hippocampus and to repair behavioral deficit. Pieces of brain tissue containing the nucleus basalis magnocellularis (NBM) or the striatum were taken for grafting from 17-day rat fetuses. About 3 months after transplantation, the rats with bilateral NBM grafts showed significant amelioration in radial-arm maze performance and habituation to a novel environment in an open field box, although they had not recovered to the control level. In rats with NBM grafts that showed a good performance, there were surviving grafts and many ingrowths of AChE-positive fibers in the hippocampus. By contrast, rats with striatal grafts showed hardly any significant improvement in these behavioral measures. The AChE staining revealed poor outgrowth of the striatal grafts into the hippocampus. These results indicate that grafting of NBM cholinergic neurons, which are anatomically similar to septal neurons, into the hippocampus produces a partial restorative effect on the cognitive impairment associated with hypofunction of the septohippocampal system.

正誤訂正

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P-492 - Effect of SM-10888 on AF64A-induced impairment of radial-arm maze learning in rats

P-492 - Effect of SM-10888 on AF64A-induced impairment of radial-arm maze learning in rats

Deficits in radial-arm maze learning in aged rats

The present study was designed to investigate the possible deficits in the place learning on the 8-arm radial maze in aged rats. In this task, reward was given in the 4 predetermined arms. Aged rats (27 months old, N = 7) acquired this task more slowly than young rats (12 months old, N = 11), and didn't reach to the performance level of the young rats within 80 training trials. Analysis of error choices revealed that the aged animals first entered in the unbaited arms more often than the young rats, whereas there was no difference in the number of re-entered choices to the baited and unbaited arms between the aged and young animals. Therefore, it was concluded that learning deficits in aged rats were attributed to deficits in the reference memory but not in the working memory.

Neonatal 6-hydroxydopamine-induced dopamine depletions: Motor activity and performance in maze learning

Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.

Impaired Biel and radial arm maze learning in rats with methylnitrosourea-induced microcephaly

Jc1:SD rats were given methylnitrosourea (MNU; 5 mg/kg, IP) on day 13 of gestation. Male offspring with MNU-induced microcephaly were examined on the Biel water maze and its mirror-image maze at 6 weeks of age and on a radial eight-arm maze at 14 weeks of age. The MNU rats showed postnatal depression in body weight. Their brain weight was about 60% of the control value, and they were thus microcephalic. The MNU animals made significantly more errors on the Biel maze and its mirror-image maze than the controls. In the radial arm maze test, they required more trials to acquire the learning criterion than the controls, and the animals with the acquired learning criterion were fewer. In the retest, however, no significant difference appeared in number of trials required for reacquisition of the criterion between the MNU and control animals. The autopsy of the MNU animals revealed the thinned cerebral cortex and hypoplastic hippocampus. The present results with the MNU rats confirmed the learning impairment and suggested no effect of microcephaly on retention of the acquired memory.

Learning impairment in the radial-arm maze following prolonged cannabis treatment in rats.

Chronic oral administration of cannabis extract to rats (daily delta 9-tetrahydrocannabinol dose 20 mg/kg) was examined in three experiments for its residual effect on radial-arm maze learning following a 1-month drug-free period. Learning a simple eight-arm maze was significantly impaired in rats treated for either 6 months (Experiment I) or 3 months (Experiment II) with the drug. In Experiment III, animals that received the extract for 3 months exhibited significant learning deficits on a much more difficult 12-arm radial maze. The results demonstrate that the deleterious effects of cannabis on radial-arm maze learning are probably due to a tendency toward increased vigilance and perseveration, possibly combined with an impaired utilization of spatial cues.