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[The development of water maze-learning ability in rats. (2) Effect of pretraining with the water-filled straight channel].

To determine whether pretraining with the water-filled straight channel affects learning acquisition, we studied the water filled multiple T-maze learning ability in 8-weeks-old SPF Wistar-Imamichi rats. The performance time for the straight channel was markedly shortened at the 2nd and 3rd trial compared to the time at the 1st trial on the 1st day. But at subsequent trials on days 2 and 3 it was longer than at the 3rd trial on day 1. At the 1st trial on day 1, the performance time of the group unexperienced in the straight channel was more than three times that of the experienced group. In subsequent trials, however, both groups showed similar performance times. More errors were observed in the unexperienced group than in the experienced group at the 1st trial on day 1. No difference was found between the two groups in subsequent trials. These results indicate that the learning acquisition was largely influenced by pretraining in the straight channel at the 1st trial on day 1.

Animals↗

Repetitive dextromethorphan at adolescence affects water maze learning in female rats.

Effects of repetitive dextromethorphan at adolescence on a spatial learning of rats were investigated. Rats received 10 daily injections of dextromethorphan (40 mg/kg) from postnatal day 28 thru 37, and were then subjected to the Morris water maze task from day 38. Significant impairments were found in the probe trial and the reversal training of the maze learning in the female rats, but not in males, treated with dextromethorphan. This result suggests that repetitive dextromethorphan, that is, abuse of dextromethorphan, at adolescence may induce deficits in the hippocampus-based memory function, perhaps more obviously in females.

Age Factors↗

Scopolamine during the paradoxical sleep window impairs radial arm maze learning in rats.

It has been proposed that there are paradoxical sleep windows (PSW) during which REM sleep is required for effective learning. Thus, rats deprived of REM sleep during 0-4 (but not 5-8) h after training show impaired learning of a radial maze task. As cholinergic (ACh) systems are active during REM sleep and may be involved in learning, this experiment investigated the effects on learning of pharmacological manipulation of the cholinergic system during the period identified as the PSW. Sprague-Dawley rats were randomly assigned to groups that were physically deprived of REM for 4 h either immediately after training or beginning 4 h after training or treated with the ACh receptor antagonist scopolamine (0-0.4 mg/kg at 0 and 2 h after training or 0.006 mg/kg at 4 and 6 h after training) on each of 9 days of radial maze training. Post-training REM deprivation (0-4 h but not 5-8 h after training) and scopolamine dose-dependently impaired learning. Results suggest that REM sleep and intact ACh neurotransmission are required during the PSW for rats to learn the radial maze task.

Animals↗

Effects of long-term ovariectomy and estrogen treatment on maze learning in aged mice.

Spatial memory deficits occur earlier in female than male rodents as the animals age, and the cessation of estrous cycle has been suggested to play a role in this phenomenon. We examined the effects of long-term ovariectomy (OVX) and estrogen replacement therapy (ERT) with subcutaneous 17beta-estradiol minipellets on maze learning in aged (24-month-old) female C57BL/6J mice using a win-stay task (1/8 arms baited) in the radial arm maze (RAM) and a position discrimination task in the T-maze. ERT was started 40 days before the behavioral tests both in gonadally intact (sham-operated) and OVX mice. The effect of early OVX on RAM performance was investigated using three different age groups (7, 11 and 24 months) with different OVX durations (4, 8 and 19 months, respectively). ERT reduced the number of reference memory errors in RAM in aged sham-operated and OVX mice, but unlike in young mice (Heikkinen et al., 2002) it had no effect on working memory errors. Furthermore, OVX impaired the performance of aged mice in the T-maze. Comparison across the three age groups and three OVX durations indicated that the memory impairment induced by an early age OVX attenuates as the mice get close to their estropausal age.

Aging↗

Water maze learning in rats with neocortical and hippocampal lesions.

Experiments were carried out in order to determine whether groups of rats (N = 7) with unilateral or bilateral ablation of the neocortex or with removal of the neocortex plus the hippocampus of either hemisphere could learn to escape from a tank of water (57 cm in diameter) climbing a visible platform when trained for 6 consecutive days. Comparison of the swimming escape latencies among groups showed no statistically significant differences, although over the first four trial blocks the decorticate group was slower (77.19 +/- 39.31, 52.45 +/- 32.37, 31.18 +/- 13.62 and 15.74 +/- 10.94 s, respectively) than the other groups, whose latencies ranged from about 70 s (the longest in the first trial block) to 8 s (the longest in the fourth trial block). Nevertheless, hemi- and bilaterally decorticate rats were still able to learn the water maze task. The same was observed for hemidecorticate plus hemihippocampectomized rats. These results indicate that the neocortex, and the hippocampus in the absence of the neocortex, is not essential for spatial localization using a cue-learning strategy.

Animals↗

The effects of cerebellar damage on maze learning in animals.

The role of the cerebellum in spatial learning has recently been investigated in genetically and non-genetically lesioned animal models, particularly in water mazes, in view of the minimal impact such lesions exert on swimming movements. A dissociation between place and cued learning in the Morris water maze has been observed in several models, including cerebellar mutant mice (Rora(sg), Nna1(pcd-1J), nervous), rats with lesions of either the lateral cerebellar cortex or the dentate nucleus, and rats with selective Purkinje cell loss caused by intracerebroventricular injections of OX-7-saporin, confirming the hypothesis that cerebellar damage may cause a cognitive deficit independently of fine motor control. In addition, the results of hemicerebellectomized rats indicate the probable involvement of the cerebellum in working memory and the procedural aspect of maze learning. The findings of impaired maze learning in cerebellar-lesioned mice and rats are concordant with those of deficient visuospatial functions in patients with cerebellar atrophy. The spatial deficits may be ascribed to altered metabolic activity in cerebellar-related pathways.

Animals↗

The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning.

The hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning was evaluated. Maze performance was studied in rats receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a T-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Rats with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms.

Animals↗

Pre-natal administration of diazepam improves radial maze learning in mice.

A number of studies have found that the peri-natal exposure of rodents to diazepam alters their adult behaviour. Adult male mice, treated with diazepam or appropriate controls during pregnancy, were examined in terms of their ability to learn a radial maze. Those animals receiving diazepam prior, but not after birth, learnt the maze significantly more rapidly. The results are discussed in terms of the possible involvement of the hippocampus in this influence of diazepam.

Age Factors↗

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 (microg/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.

Animals↗

Non-spatial water radial-arm maze learning in mice.

Recently, we published a method for examining working and reference memory in mice using a spatial version of the water radial-arm maze. Here we describe a non-spatial version of the same maze. BXSB mice were able to learn the maze as shown by the decrease in the number of working and reference memory errors over sessions. This maze was used to examine learning differences between males and females and between mice with misplaced clusters of neurons in layer I of cortex (ectopias) and those without. In a prior study using the spatial version of the water radial-arm maze, male BXSB mice had poorer working memory than females during the acquisition phase. Similarly, in this study male BXSB mice demonstrated impaired working memory during the asymptotic phase of non-spatial radial-arm maze learning. Two prior studies showed that mice with neocortical ectopias demonstrated working memory impairments compared to non-ectopic littermates in the spatial version of the water radial-arm maze. Contrary to this, in the non-spatial radial-arm maze used here, ectopic mice were not impaired in working memory and showed better memory when the working memory 'load' was the highest. Overall, both versions of the maze can be useful tools to assess spatial and non-spatial working and reference memory in mice.

Animals↗

Caudate nucleus stimulation retroactively impairs complex maze learning in the rat.

Rats, with permanent electrodes implanted bilaterally in the caudateputamen complex, were stimulated with single pulses after reinforcement of each maze learning trial or were stimulated with multiple pulses after each choice point or after reinforcement. Single pulses retarded the development of learning only when stringent learning criteria were required, whereas multiple pulses interfered with acquisition when the criteria for learning were less difficult.

Age Factors↗

[Y-maze learning in two strains of mice. Effects of instrumental and pharmacologic sleep deprivation].

Effects of instrumental and pharmacological deprivation of sleep on Y-maze learning have been studied in two inbred strains of mice (C57BR/cd/Orl and C57BL/6/Orl), having identical sleep rhythms, but mainly differing in their ability to learn. Administration of alpha-methyl-DOPA (100 mg/kg) provokes complete suppression of paradoxical sleep (PS) for 9-11 h. Injection immediately after each training session over the first 5 days caused a delay in acquisition of an active avoidance task in C57BR mice. Treated C57BL/6 mice exhibited a significant facilitation of acquisition. Similar results were obtained by instrumental deprivation of sleep for 10 h.

Animals↗

Impaired maze learning and cerebral glucose utilization in aged hypertensive rats.

To elucidate the effects of prolonged hypertension on brain function during aging, we examined learning of an eight-arm radial maze task and local cerebral glucose utilization in young-adult (3 to 4 months old) and aged (16 to 17 months old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Young-adult SHR learned the task more slowly than young-adult WKY, but cerebral glucose utilization, measured by the [14C]2-deoxyglucose method in 24 brain structures, was not significantly different in the two groups. The aged SHR and WKY exhibited impaired learning ability. Cerebral glucose utilization was reduced (13% to 23%) in six regions in aged WKY and in 12 regions in aged SHR compared with values in the respective young-adult groups. Furthermore, the aged SHR showed a greater disturbance of learning acquisition and more profound reduction of cerebral glucose utilization in five regions than the aged WKY. In SHR, hypometabolism, indicated by a decrease in glucose utilization in 15 brain structures including the cerebral cortex, hippocampus, and visual system, was significantly correlated with impaired learning acquisition, indicated by an increase in total error choices. These findings show that (1) hypertension per se does not impair maze learning or cerebral glucose utilization in young-adult rats, and (2) brain function is impaired during aging and prolonged hypertension is an additional factor facilitating brain dysfunction associated with neuronal hypoactivities, resulting in behavioral deterioration including learning disability. Thus, early control of hypertension seems important for preventing or reducing brain dysfunction in senescence.

Aging↗

Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains.

Correlations between the densities of ionotropic glutamate, GABA(A), and serotonin binding sites in the hippocampus of seven inbred mouse strains and strain-specific learning capacities in two types of maze were studied. Binding site densities were measured with quantitative receptor autoradiography. Learning capacities were determined in a water maze task as well as in spatial and nonspatial versions of an eight-arm radial maze. The densities of most binding sites differed significantly between the strains in the subfields of Ammon's horn (CA1 and CA3) and the dentate gyrus, except for serotonin binding sites in CA1. By comparing the different strains, significant receptor-behavioral correlations between the densities of the GABA(A) receptors and the activity-dependent behavior in the water maze as well as the spatial learning in the radial maze were found. The densities of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (AMPA) and kainate receptors correlated positively with learning capacity in the spatial eight-arm radial maze. We conclude that hereditary variations mainly in AMPA, kainate, and GABA(A) receptor densities are involved in behavioral variations in spatial and nonspatial learning tasks.

Analysis of Variance↗

Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse.

BACKGROUND: The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). RESULTS: Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. CONCLUSION: Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models.

Journal Article↗

Intrahypothalamic microinjections of noradrenaline with and without induction of the alimentary drive as a reward in a T maze learning in rats.

Noradrenaline injected into the perifornical region of the anterior part of the lateral hypothalamus in rats can serve as a reinforcement in a T maze learning, whether it induces the activation of the alimentary drive or not. It follows that the main role of noradrenaline in this brain area consists not so much in induction of the alimentary drive as in activation of the very process which is essential for the reinforcement. It is claimed that intrahypothalamic microinjections of noradrenaline evoke pleasurable states which constitute a virtual reinforcement of motivated behavior.

Animals↗

The compensatory role of food-motivation in the maze learning performance of lactationally undernourished rats.

To test the hypothesis that the motivational effects of neonatal undernutrition might conceal the detrimental effects on learning, we tested previously undernourished and normally nourished Sprague-Dawley rats on learning of a novel maze pattern under either latent learning (nonappetitive) or food-motivated conditions. Under the nonappetitive conditions, the previously undernourished rats learned significantly less than the normal controls, but when motivated for food, the undernourished rats performed as well as the controls. When learning performance measures are sensitive to motivation, differential motivation between undernourished and normal subjects must be controlled or eliminated.

Animals↗