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Open-field behaviors and water-maze learning in the F substrain of Ihara epileptic rats.

PURPOSE: Genetically epileptic model rats, Ihara epileptic rat (IER/F substrain), have neuropathologic abnormalities and develop generalized convulsive seizures when they reach the age of approximately 5 months. Because the neuromorphologic abnormalities are centered in the hippocampus, we expected to observe spatial cognitive deficits. The present study aimed to evaluate emotionality and learning ability of the F substrain of IER. METHODS: To determine whether deficits are caused by inborn neuropathologic abnormalities or by repeated generalized convulsions, we tested nine 6- to 12-week-old IER/F rats that had not yet experienced seizures (experiment 1) and nine 7- to 9-month-old IER/F rats that had repeatedly experienced seizures (experiment 2) with identical tasks: an open-field test and the Morris water-maze place and cue tasks. RESULTS: Both groups of IER/Fs showed behaviors that were different from those of control rats in the open-field test, and extensive learning impairments were seen in both the place task, which requires spatial cognition, and the cue task, which does not require spatial cognition but requires simple association learning. Their impaired performance of the cue task indicates that their deficiency was not limited to spatial cognition. CONCLUSIONS: Because young IER/F rats without seizure experiences also showed severe learning impairments, genetically programmed microdysgenesis in the hippocampus was suspected as a cause of the severe learning deficits of IER/Fs.

Age Factors↗

Demands during maze. learning in limbic epileptic rats: selective damage in the thalamus?

A qualitatively evident enhancement of chromolytic neurons within the lateral posterior thalamus of rats in which limbic seizures had been induced by lithium and pilocarpine and who were later trained for spatial memory was assessed quantitatively. The significant increase in the numbers of chromolytic neurons and the decrease in the numbers of normal neurons for these rats compared to the reference brains suggested these morphological changes were recent. The hypothesis that excessive stimulation of the lateral posterior nucleus by daily training in a radial maze may have facilitated the necrosis was supported by the inverse relationship between a linear combination of the numbers of normal neurons and oligodendroglia and the rate of learning during the earlier but not the later sessions. An implication for iatrogenic effects from rehabilitation of humans following brain injury was suggested.

Animals↗

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

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.

Animals↗

An analysis of factors influencing complex water maze learning in rats: effects of task complexity, path order and escape assistance on performance following prenatal exposure to phenytoin.

Three hypotheses on factors determining performance in a complex water maze were tested in rats prenatally exposed to phenytoin. The hypotheses were: 1) that increasing maze complexity would better differentiate experimental effects; in particular, that an expanded version of a maze originally described by Biel would better differentiate groups than Biel's original design; 2) that path order is an important factor determining performance; specifically, that path sequence AB would better differentiate experiments from controls than the opposite order (sequence BA); and 3) that repeated trial failures interfere with learning, a problem putatively prevented by employing assisted (i.e., guided) escape. The specific prediction was that rats tested with assisted escape would learn faster and produce better group differentiation than rats tested with unassisted escape. Pregnant female Sprague-Dawley CD rats were gavaged on days 7-18 of gestation with propylene glycol alone (Control) or containing 100 or 200 mg/kg of phenytoin. Straight channel swimming trials followed by maze trials were begun on separate male/female offspring pairs from each litter on postnatal days 50, 70, or 90. The results confirmed hypothesis 1, i.e., the more complex maze better differentiated phenytoin-related group differences. This was true regardless of whether the phenytoin rats exhibiting circling were included in the analyses or not. The results disconfirmed hypothesis 2, i.e., that path order AB would better differentiate the groups than path order BA. Rather, the data supported the alternate hypothesis, that path order was not a significant determinant of prenatal drug-related maze deficits. This was unchanged regardless of whether phenytoin offspring exhibiting circling were or were not included in the analyses. The implication is that path B alone was sufficient to detect phenytoin's effects on maze performance. Finally, the overall results disconfirmed hypothesis 3, i.e., assisted escape failed to differentiate groups any better than unassisted escape regardless of whether circlers were or were not included in the analyses. However, when more detailed analyses were performed only on rats that failed to find the goal on the first or second trials of path B, an assistance effect was noted. The effect (fewer errors) only occurred in the controls and only on the first two trials of path B. It was concluded that assisted escape was, at best, a minor contribution to improved maze performance.

Animals↗

The effect of cul length and hippocampal lesions on maze learning in the rat.

Twenty-four rats, 8 with bilateral hippocampal lesions, 8 with cortical lesions and 8 unoperated rats, were tested on one of 2 mazes. Half of each group were run in a conventional 5 choice multiple Y maze. The other half were run in a symetrical, long cul maze in which distance and number of successive choice point were equal for a right or wrong choice before the animal reached an cul end or the goal box. The correct path in the long cul maze was identical to that of the short cul maze. S's were run one trial a day for 15 days. On the symetrical, long cul maze there were no differences between groups. On the short cul maze, hippocampals were significantly worse than control S's and looked similar to control S's on the long cul maze. The results are interpreted in terms of frustration theory.

Animals↗

An attempt to use central dopaminergic stimulation as a reinforcement for T-maze learning in rats.

Two groups of 8 rats with unilateral cannulas aimed at the lateral hypothalamus (LH) or nucleus accumbens (nAcc) were trained in a T-maze to receive intracerebral injections of dopamine as a reinforcement for choosing the proper arm of the maze. Neither in the LH nor in the nAcc groups did dopamine show evident reinforcing properties comparable to those found earlier for noradrenaline.

Animals↗

Acquisition of dominance status affects maze learning in mice.

Learning is likely to be costly and thus subject to trade-off with other components of life history. An obvious prediction, therefore, is that investment in learning, and thus learning performance, will vary with individual life history strategy and the reproductive value of the learning outcome. We tested this idea in the context of social dominance in male laboratory mice, using a simple radial maze paradigm to compare the ability of high- and low-ranking male mice to track changing food location. We tested animals in randomly selected pairs before and after establishing aggressive rank relationships to distinguish intrinsic differences in learning ability from those attributable to acquiring high or low rank. There was no difference in learning between later dominants and subordinates prior to establishing rank relationships. After pairing, however, dominants showed a significantly greater percentage of correct responses, with the difference being greatest earlier in a sequence of trials. The percentage of correct responses also increased with the amount of aggression initiated during pairing. The results thus appeared to reflect a state-dependent change in learning associated with the aggressive social relationships formed during pairing.

Journal Article↗

The effect of early visual experience on spatial maze learning in rats.

In the 1st of 2 experiments on spatial ability, groups of sighted and blind, light-reared (LR) and dark-reared (DR) rats were tested on a series of (Hebb-Williams) maze problems and their reversals under appetitive and aversive reinforcement conditions. Significant effects due to early rearing conditions, vision at time of testing, and problem were found. Dark-reared rats learned the problems whose solution depended on nonvisual cues more slowly than LR animals. Blindness at time of testing had a significantly adverse effect on the performance of LR and DR rats on all problems, but a significantly greater effect in the DR animals. In a 2nd experiment DR rats were also found to perform less effectively than LR rats on a 17-arm radial maze throughout a 36-day period during which variations in the task were introduced. The results reveal the impact of early visual experience on the development of the ability to acquire spatial concepts.

Animals↗

Maze learning by adult rats after inhibition of neuronal multiplication in utero.

Rats whose mothers received hydroxyurea (HU, 1 or 2 g/kg) at 14 days of gestation had a 30% deficit in both brain and body weight at birth, when compared with controls. Number of brain cells at birth (mainly neurons) was reduced by 33-34%. A severe reduction in postnatal whole brain growth (31-33% in adulthood) was observed, but the cerebellum was relatively spared. In the Hebb-Williams maze text in adulthood HU animals made 28% more errors than controls over 12 problems. The differences were much more marked on certain problems and for HU animals with particularly small brains. In a T-maze spatial discrimination test in adulthood HU rats learned the initial response normally but, when required to reverse this response, showed a significant tendency to make more perseverative errors than controls.

Animals↗

Neuroanatomical divergence between two substrains of C57BL/6J inbred mice entails differential radial-maze learning.

Compared to the parental strain C57BL/6J, male mice from the mutated substrain C57BL/6JNmg show smaller hippocampal intra- and infrapyramidal mossy fiber projections and a correlated inability to master a simple spatial radial-maze task. Possibly, these two substrains differ for only one single gene, making them a valuable model to investigate the physiological pathways leading from genotype to neurobehavioral phenotype.

Animals↗

Selective lesioning of forebrain noradrenaline neurons at birth abolishes the improved maze learning performance induced by rearing in complex environment.

The effect of selective destruction of forebrain noradrenaline (NA) neurons induced by 6-hydroxydopamine (6-OHDA) at Day 1 after birth on Hebb-Williams maze performance was investigated in adult rats housed after weaning in a complex environment (EC) or an isolated (IC) environment for 35 days. Saline treated control rats raised in the EC made fewer errors than those raised in the IC. This effect of EC was completely abolished in 6-OHDA treated rats; for these animals no improved performance due to the housing condition was obtained. Protection of the NA neurons against 6-OHDA neurotoxicity by pretreatment with desipramine (DMI) resulted in an effect of EC identical to that seen in saline-treated controls. Postweaning housing in the IC led to an increased locomotion as compared to housing in EC, but this effect was not affected by neonatal 6-OHDA and/or DMI treatment. Neurochemical analysis confirmed cortical NA and metabolite depletion as well as a good protection by the DMI pretreatment. The present results indicate that central NA neurons are involved critically in mediating mainly the cognitive components of behavioral alterations induced by EC.

Animals↗

Age-related impairment in complex maze learning in rats: relationship to neophobia and cholinergic antagonism.

Scopolamine was utilized to assess cholinergic muscarinic blockade on the performance of young (3 months) and aged (23 months) male F-344 rats in a 14-unit T-maze task. Prior to training, a portion of each age group received a gustatory neophobia test (percent consumption of a novel sucrose solution) to assess involvement of norepinephrine systems implicated in age-related impairments of rats in other memory tasks. All rats were pretrained in one-way active avoidance (1.0 mA) on 3 consecutive days. Rats meeting criterion (8/10 avoidances on last day) began maze training the next day consisting of 10 trials on 2 consecutive days. The task required the rat to negotiate each of 5 maze segments within 10 sec to avoid scrambled footshock (1.0 mA). Rats received an intraperitoneal injection of either scopolamine hydrochloride (0.5 mg/kg or 0.75 mg/kg) or saline vehicle 30 min prior to maze testing. Consistent with past reports, aged rats were more neophobic (i.e., consumed less sucrose) than were young rats, but the degree of neophobia was not significantly correlated with maze error performance in either age group. Also consistent with previous studies, aged rats were significantly impaired, compared to young counterparts, in all maze performance measures including errors, alternation errors, runtime, and shock frequency and duration. Significant scopolamine-induced deficits were observed in both age groups, but only in errors and alternation strategy. No age by drug interaction was manifested in any performance measure indicating that scopolamine impaired learning of young and aged rats equivalently.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Exploration, fear and maze learning in spontaneously hypertensive and normotensive rats.

In this study the performance of normotensive (WKY) rats was compared with that of hypertensive (SHR) rats on a Novel Object Test, a standardized Fear Test, and the Hebb-William's maze. We found no strain differences for exploration; however, WKY rear and ambulate more than SHR near the walls of the apparatus. There were no strain differences apparent in the Fear Test. WKY showed markedly different behavior compared with SHR on the Hebb-William's maze; WKY showed a high level of stereotyped displacement behaviors and failed to improve their performance over successive trials. Overall, WKY appear to be more reactive to environmental conditions than SHR. The behavior of both strains is highly context dependent.

Animals↗

Comparative effects of long-term ethanol consumption and forebrain lesions on maze learning and active avoidance behavior in rats.

Male rats consumed a liquid diet containing 10.7% ethanol as their only source of food and fluid for 6.5 months, beginning at 2 months of age. During withdrawal, there were no differences between the alcohol group and their pair-fed or free-fed controls on EEG, body temperature, irritability and tremor measures. In behavioral tests begun 4-5 weeks after withdrawal, the rats that had consumed alcohol acquired accurate spatial behavior in a cross maze task more slowly than controls, but were unimpaired in shuttle-avoidance learning. In concurrent studies with groups of rats that had sustained lesions of the dorsal hippocampus, the mamillary bodies (MMB), or the mediodorsal thalamus, the pattern of behavioral deficits after MMB lesions was found to be qualitatively similar to that observed after the cessation of long-term alcohol consumption. These findings provide renewed hope that a useful rodent model for studying the neuropsychology of cognitive deficits associated with human alcoholism can be developed.

Alcoholism↗

Brain lesions and water-maze learning deficits after systemic administration of kainic acid to adult rats.

The relationship between hippocampal damage and spatial learning deficiencies was studied in rats injected with kainic acid (10 mg/kg i.p.). A single injection was given either before or after the acquisition phase of the Morris water-maze task. In this acquisition phase, the animals were required to find a hidden underwater platform starting from four different points. The task was repeated twice a day for 10 days. In the retention phase after 10 days rest, the rats repeated the same task. The damage caused by the treatment occurred in several prosencephalic areas, including the piriform and enthorhinal cortices, the thalamus and the hippocampus. In the latter, greatest damage was seen in CA1 followed by CA3 while CA2 and the gyrus dentatus appeared almost unaffected. The behavioural results indicated that kainic acid impaired but did not preclude the acquisition of the water-maze task. During the retention phase, no significant differences in latencies were found between animals that were treated before and after acquisition, thus, indicating that pretraining does not play an important role in the recovery of these spatial abilities following hippocampal lesions.

Animals↗

Sex-dependent effects of neonatally administered morphiceptin and D-ala-D-leu-enkephalin on maze learning in rats.

Newborn rats were injected (ip) with morphiceptin [72.7 micrograms/kg (a mu-type opioid receptor agonist)], D-alanine2-D-leucine5-enkephalin [79.4 micrograms/kg (a delta-receptor agonist)], or saline for 7 days after birth. Testing on a complex maze on Day 25 revealed a significant sex-dependent facilitation of performance by the opioid peptides. Peptide-treated females performed better than the males on the first day of training as measured by errors. Opioid treatment increased mortality, as three times as many peptide-treated animals died in comparison to the saline control group. Peptide treatment did not affect locomotor activity measured in an open field. Weight at Day 24 was also affected by the peptide treatment, females and males injected with the opioids being lighter and heavier, respectively, than the control group.

Animals↗