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Maze learning in rats: a comparison of performance in two water mazes in progeny prenatally exposed to different doses of phenytoin.

Pregnant Sprague-Dawley CD rats were administered phenytoin by gavage on days 7-18 of gestation in doses of 0, 100, 150 and 200 mg/kg. At 46-53 days of age rat offspring in each litter were divided with half tested in a Biel water maze and half in a new, more complex water maze. On the first test day all rats were tested in a straight channel. On subsequent days rats received 5 trials in the Biel maze or 6 trials in the new maze in path A, followed by 6 trials in path B (in which the start and goal positions were reversed). Analyses showed that phenytoin increased offspring mortality shortly after birth at the highest dose, but did not affect growth at any dose. Phenytoin had no effects on straight channel swimming performance. Analyses of maze performance showed that both mazes differentiated phenytoin offspring from controls, but that the new, more complex maze distinguished the groups more definitively. Maze errors also showed a clear dose-response relationship in the new maze, while no such distinctions were seen in the Biel maze. It was concluded that the new maze design may offer significant gains over the Biel maze in terms of detection sensitivity to prenatally induced CNS injury.

Animals↗

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.

Animals↗

[Asymmetry of movement direction of Myrmica rubra ants during maze learning motivated by food].

Asymmetry in direction of motion was found in Myrmica rubra ants at their learning in a symmetrical multi-alternative maze in conditions of "social" alimentary motivation. It was manifested in the form of preferable stay in the right half of the maze and was significant by several parameters: total number of motions, approaches to "false" spots and right turns. Unequal degrees of spatial-motor asymmetry (individual and for the whole sample) was revealed by various parameters. Most clearly the right-sided spatial preference was seen in the insects which had more approaches to goal with reinforcement taking than "exploratory" approaches. It is suggested that the parameters of motion direction asymmetry in ants learning in the maze depend on the level of alimentary "social" motivation.

Animals↗

Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats.

The pharmacological properties of MKC-231 (2-(2-oxopyrrolidin-1-yl)-N- (2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl) acetoamide, CAS 135463-81-9) in comparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40-8) were studied. MKC-231(10(-10)-10(-6) moll) significantly increased high affinity choline uptake (HACU) when it was incubated with the hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but not of normal rats. MKC-231 did not affect the AChE activity, [3H]- quinuclidinyl benzilate binding, and [3H]-pirenzepine binding. Oral administration of MKC-231 (1-10 mg/kg) significantly improved the learning deficits in the Morris' water maze of AF64A-treated rats, but it did not produce any significant side effects, like tremor, salivation or hypothermia, which were observed in rats treated with high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed to ameliorate the learning deficits in AF64A-treated rats. These results suggest that MKC-231 is a novel and quite unique compound, which improves the memory impairment induced by AF64A through the enhancement of HACU without any side effects at the effective doses.

Acetylcholinesterase↗

Impaired water maze learning performance in mu-opioid receptor knockout mice.

Previous study has demonstrated that the lack of mu-opioid receptor decreased LTP in the dentate gyrus of the hippocampus, suggesting the possibility that the lack of mu-opioid receptor may accompany a change in learning and memory. However, no behavioral study has been undertaken to correlate LTP deficits with spatial memory impairment in mu-opioid receptor knockout mice. Therefore, the present study investigated the hypothesis that mu-opioid receptors contribute to learning and memory by using the Morris water maze, and comparing responses in wild type and mu-opioid receptor gene knockout mice. Our results indicated that mu-opioid receptor knockout mice showed a significant spatial memory impairment compared to wild type in the Morris water maze. This result suggests that the expression of mu-opioid receptor plays an important role in spatial learning and memory examined by Morris water maze.

Animals↗

Spatial and nonspatial Morris maze learning: impaired behavioral flexibility in mice with ectopias located in the prefrontal cortex.

About half of BXSB/MpJ-Yaa (BXSB) mice have neocortical ectopias (misplaced clusters of neurons located in layer I of cortex). Previous behavioral studies have suggested that ectopic mice have superior spatial, but equivalent nonspatial, reference memory learning. However, since spatial and nonspatial learning were not assessed in the same apparatus and with the same testing procedure, it is unclear if this conclusion is accurate. We have created a new nonspatial Morris maze for mice that differs from the spatial task only in the type of cues that must be utilized to efficiently locate the platform (intra-maze black/white patterns vs. extra-maze room cues) and does not differ in the level of task complexity or the presence of objects within the maze. Ectopic mice were very good in utilizing extra-maze cues when learning the spatial version and in utilizing intra-maze cues when learning the nonspatial version of the Morris maze, while non-ectopics were not, suggesting that ectopics have superior spatial and nonspatial reference memory. Ectopias in BXSB mice are usually located in prefrontal and/or motor cortex. The prefrontal cortex is involved in behavioral flexibility (e.g. being able to easily switch from using spatial to nonspatial cues). Only ectopic mice with ectopias specifically located in the prefrontal region of cortex demonstrated difficulty switching from using extra-maze to intra-maze cues and vice versa. Thus, the presence of one or more ectopias in the prefrontal region of cortex disrupted one of the normal functions of the prefrontal cortex.

Animals↗

Protein tyrosine phosphatase alpha (PTP alpha) knockout mice show deficits in Morris water maze learning, decreased locomotor activity, and decreases in anxiety.

Receptor PTPalpha is a widely expressed transmembrane enzyme enriched in brain. PTPalpha knockout (PTPalpha(-/-)) mice are viable and display no gross abnormalities. Brain and embryo derived fibroblast src and fyn activity is reduced to <50% in PTPalpha(-/-) mice. These protein kinases are implicated in multiple aspects of neuronal development and function. However, the effect of the loss of function of the PTPalpha gene on behavior has yet to be investigated. PTPalpha(-/-) and WT mice were tested for anxiety, swimming ability, spatial learning, cued learning, locomotor activity, and novel object recognition (NOR). PTPalpha(-/-) mice were indistinguishable from WT in swimming ability, cued learning and novel object recognition. Knockout mice showed decreased anxiety without an increase in head dips and stretch-attend movements. During Morris water maze (MWM) learning, PTPalpha(-/-) mice had increased latencies to reach the goal compared to WT on acquisition, but no memory deficit on probe trials. On reversal learning, knockout mice showed no significant effects. PTPalpha(-/-) mice showed decreased exploratory locomotor activity, but responded normally to a challenge dose of D-methamphetamine. The data suggest that PTPalpha serves a regulatory function in learning and other forms of neuroplasticity.

Animals↗

Maze learning and morphology of frontal cortex in adult and aged basal forebrain-lesioned rats.

Maze performance and morphology of frontal cortex were assessed in young adult, middle-aged, and aged rats with and without lesions of the nucleus basalis magnocellularis. Although maze performance did not vary with age, neuron number and the thickness of superficial laminae were reduced in aged rats. Lamina II-III neurons were hypertrophied in middle-aged rats relative to both younger and older groups. At all ages, lesions significantly impaired maze performance. In young adult rats, lesions moderately reduced the size of lamina II-III neurons. This effect was more pronounced in middle-aged rats. Lesions in aged rats did not affect neuron size. The neuronal changes seen in middle-aged rats may reflect a compensatory response to the expression of other age-related neuronal changes, which may affect the ability of cortical neurons to respond to lesion-induced loss of cholinergic input.

Afferent Pathways↗

Impairment of water maze behaviour with ageing is counteracted by maze learning earlier in life but not by physical exercise, food restriction or housing conditions.

Spatial learning and memory decline with ageing in humans as well as rats. We examined the influence of different interventions on male Sprague Dawley rats with respect to learning ability and memory at the age of 5, 10 and 18 months. The intervention and control groups were: (RW) voluntary exercise in running wheels, (PW) sedentary, food restricted (by about 25%) to keep them at pair weight with RW, (S1) sedentary, fed ad libitum, (TM) forced training in a treadmill, and, (S4) sedentary, fed ad libitum. The animals in all groups were housed individually except those in group S4, which were housed four in each cage. The ability of learning and memory was determined in the Morris water maze. The results showed a significantly better learning ability when young in comparison with their ability when having grown older. At the age of 18 months, the performance was significantly better in the subgroups which had received training also at the age of 10 months compared to the subgroups receiving their first training. None of the various interventions had any significant effect on these functions. Repeated training seems to be the best intervention with respect to retaining learning ability and memory.

Aging↗

Test for effects of visual and position cues on T-maze learning in toads.

This research was concerned with the effects of different classes of cues on the ability of toads (Bufo marinus) to learn an escape task, discrimination learning, in a T-maze. The cues were either a black or white brightness cue, a right or left position cue, or combinations of brightness and position cues. The toads were given a .6-A shock until they made the correct response. Results suggested that toads are capable of learning a discrimination task based on either a position or brightness cue. However, the rate of learning was influenced by strong aversion to the white arm when escaping from an aversive stimulus. No particular preference for either brightness or position cues was found independent of this aversion.

Animals↗

Branched chain amino acids improve complex maze learning in rat offspring prenatally exposed to hyperphenylalaninemia: implications for maternal phenylketonuria.

Maternal phenylketonuria results in a high incidence of children born who are mentally retarded. It has been suggested that blood-brain-barrier transport of phenylalanine may be reduced by competitive inhibition of transporter uptake by supplemental administration of other large neutral amino acids. We hypothesized that large neutral amino acids might also be effective at improving the outcome of fetuses exposed to hyperphenylalaninemia in utero. If correct, sparing of embryonic CNS development might be possible. Pregnant rats were given a hyperphenylalaninemic diet alone or the same diet supplemented with a combination of valine, isoleucine, and leucine. As adults, the progeny exposed in utero to hyperphenylalaninemia showed characteristic learning deficits in a complex maze, while those exposed in utero to hyperphenylalaninemia combined with valine, isoleucine, and leucine showed no deficits in maze acquisition. The valine, isoleucine, and leucine supplement may show promise as a treatment for intrauterinely acquired mental deficiency associated with maternal phenylketonuria.

Amino Acids, Branched-Chain↗

[Ameliorating effects of idebenone and indeloxazine hydrochloride on impairment of radial maze learning in cerebral embolized rats].

The ameliorating effects of idebenone and indeloxazine hydrochloride on the impairment of memory and learning were studied in cerebral embolized rats. The embolized rats had impaired memory and learning ability in the radial maze task; these were demonstrated by a decrease in correct responses and an increase in total errors. In particular, the rats showed severe impairment of working memory, as shown by a marked increase in the numbers of re-entries into the arm that had been already visited. Idebenone (30 mg/kg, p.o.) exerted marked ameliorating effects on the impairment in the embolized rats: the drug significantly increased the correct responses and decreased the errors. Indeloxazine hydrochloride also improved the memory impairment in the embolized rats, as shown by a reduction of the errors. The ameliorating effects of these drugs may be due mainly to improvement of hypofunctions of the central nervous system. These results confirm that idebenone and indeloxazine hydrochloride may have ameliorating actions on impairment of memory and learning induced by brain hypofunction, and they suggest that the action of idebenone is more potent than that of indeloxazine hydrochloride.

Animals↗

Changes in eye-head-body movements during maze learning.

Investigation of the relationship between visual search (eye movement) and walking (head and body movement) during way-finding through a maze by each of 6 subject pedestrians who wore an eye camera showed patterns of sight lin, head movement, body movement, and changes of coordination between eye-head-body movement during the process of comprehension of the pathways were revealed.

Eye Movements↗

LATERAL HYPOTHALAMIC STIMULATION IN SATIATED RATS: T-MAZE LEARNING FOR FOOD.

It is well known that electrical stimulation in portions of the lateral hypothalamic area is positively reinforcing and induces eating in satiated rats. We have found that continuous stimulation of this kind can also motivate satiated and previously untrained rats to learn the location of food in a T-maze. Efficient acquisition and reversal of discriminations for food indicate that lateral hypothalamic stimulation exerts motivational effects which are functionally equivalent to those of food deprivation.

Brain↗

Passive avoidance and complex maze learning in the senescence accelerated mouse (SAM): age and strain comparisons of SAM P8 and R1.

Two strains of the senescence accelerated mouse, P8 and R1,were tested in footshock-motivated passive avoidance (PA; P8, 3-21 months; R1, 3-24 months) and 14-unit T-maze (P8 and R1, 9, and 15 months) tasks. For PA, entry to a dark chamber from a lighted chamber was followed by a brief shock. Latency to enter the dark chamber 24 hours later served as a measure of retention. Two days of active avoidance training in a straight runway preceded 2 days (8 trials/day) of testing in the 14-unit T-maze. For PA retention, older P8 mice entered the dark chamber more quickly than older R1 mice, whereas no differences were observed between young P8 or R1 mice. In the 14-unit T-maze, age-related learning performance deficits were reflected in higher error scores for older mice. P8 mice were actually superior learners; that is, they had lower error scores compared with those of age-matched R1 counterparts. Although PA learning results were in agreement with other reports, results obtained in the 14-unit T-maze were not consistent with previous reports of learning impairments in the P8 senescence accelerated mouse.

Age Factors↗