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PubMed1996

Differential effects of anterior and posterior insular cortex lesions on the acquisition of conditioned taste aversion and spatial learning.

In this study, we evaluated the effects of NMDA-induced lesions in different sites of the insular cortex of the rat on the acquisition of conditioned taste aversion and spatial learning in the Morris water maze. The lesions were produced by bilateral microinjections of NMDA in the insular cortex at +3.7 mm (Anterior group), +1.7 mm (Central group), and -0.3 mm (Posterior group) anteroposterior from bregma. The results showed that the central and posterior, but not the anterior, lesions disrupted the acquisition of water maze learning as measured by the high latency to reach the target. In contrast, the conditioned taste aversion learning was disrupted by lesions in the central but not in the anterior or posterior insular cortex. These data confirm functional heterogeneity of the insular cortex and demonstrate that the more caudal parts are only necessary for acquisition of the water maze task, while the central insular cortex is crucial for the acquisition of both the conditioned taste aversion learning and the Morris water maze.

Animals↗
PubMed1990

Effects of exposure period and nutrition on the developmental neurotoxicity of anticonvulsants in rats: short and long-term effects.

The results of three experiments on the functional neuroteratogenicity of anticonvulsants in rats are presented. Two of the experiments have been reported previously and are reviewed here, while the third experiment is presented here for the first time. The first experiment examined prenatal phenytoin (200 mg/kg), trimethadione (250 mg/kg), and phenobarbital (80 mg/kg) for critical period effects by exposing separate groups of rats to the drugs or to vehicle on embryonic (E) days 7-10, 11-14, or 15-18. Phenytoin produced effects in the E11-14 offspring, but few effects in the E15-18 offspring, and almost no effects in the E7-10 offspring. Phenytoin's E11-14 effects in the offspring were increased pivoting, delayed swimming ontogeny, hyperactivity, impaired water maze learning, and impaired passive avoidance retention. The second experiment looked for phenytoin's long-term effects. Phenytoin-exposed offspring administered 200 mg/kg on E7-18 exhibited numerous postnatal dysfunctions, including water maze learning deficits that persisted to beyond 501 days of age. The learning deficits were neither increased nor decreased in severity at this age compared to those seen in littermates tested at 50 days of age. The third experiment assessed the role of manganese in counteracting phenytoin-induced postnatal dysfunction and the possible confounding effects of maternal undernutrition associated with the drug's administration. The typical pattern of phenytoin-induced behavioral effects was observed in rat offspring. The results demonstrated that undernutrition was not a confound, since pair-feeding and pair-watering controls did not diminish the phenytoin-induced dysfunction in the offspring. Also, administration of a manganese supplementation (200 ppm in the drinking water) during gestation did not significantly alter the pattern of phenytoin-induced postnatal effects.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Effect of dietary docosahexaenoic acid and phosphatidylcholine on maze behavior and fatty acid composition of plasma and brain lipids in mice.

We investigated the effects of dietary docosahexaenoic acid (DHA, 22:6 n-3) and phosphatidylcholine (PC) on maze behavior and brain fatty acids in mice. Male Crj:CD-1 mice (3 wk old) were fed a diet containing 2% DHA and 3% palm oil (DHA group); 5% PC (PC group); 1% DHA, 2.5% PC and 1.5% palm oil (DHA + PC group); 5% palm oil (Palm oil control group) or MF laboratory chow (MF control group) for 7 mo. After this time maze-learning ability was assessed. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured three times every four days. After the last learning test, all mice were sacrificed and plasma and brain were analyzed for fatty acid composition. The DHA and PC groups required less time to reach the maze exit and strayed less into blind alleys than the control group in the third trial. The difference between the DHA or PC groups and control mice was statistically significant (p < 0.05). In the total lipids of plasma and brain of mice fed DHA, there was a significant increase in DHA levels and a concomitant decrease in arachidonic acid (AA, 20:4 n-6). Similar changes in fatty acid composition were observed in brain phosphatidylcholine and phosphatidylethanolamine for this group of mice. However, this pattern of changes in brain fatty acids was not evident in the PC group. Our data suggest that maze-learning ability in mice is enhanced by intakes of DHA and PC. However, the mechanisms by which the DHA and PC diets improved learning ability appear to be different. A synergistic effect of DHA and PC on learning ability is not apparent in the DHA + PC group.

Animals↗
PubMed1990

Behavioral effects of 5-HT receptor ligands in the aversive brain stimulation, elevated plus-maze and learned helplessness tests.

In order to illustrate the use of animal models in the study of the anxiolytic and antidepressant properties of drugs acting on 5-HT receptors, a series of experiments is described. With electrical stimulation of the midbrain central gray (CG), an aversive area of the brain, the 5-HT-1 receptor antagonist propranolol raised the aversive threshold in a dose-dependent way, following its microinjection into the CG. This antiaversive effect of propranolol, which is similar to that of benzodiazepine anxiolytics, was prevented by microinjection into the same brain site of the 5-HT-2 receptor blocker ritanserin. Ritanserin itself and the 5-HT-1A receptor ligand ipsapirone caused either little or no effect. In another animal model of anxiety, the elevated plus-maze, intra-CG propranolol also caused an anxiolytic-like effect, antagonized by ritanserin, indicating a 5-HT mediation. However, systemically injected isamoltane, a congener of propranolol, was ineffective in the elevated plus-maze, whereas ipsapirone caused an anxiolytic effect. Ritanserin was again inactive. Finally, both ipsapirone as well as another 5-HT-1A receptor ligand BAY R 1531, given IP, reversed the learning deficit resulting from exposure to uncontrollable foot-shocks, an effect characteristic of antidepressant drugs.

Animals↗
PubMed1989

The effects of ibotenic acid lesions of the nucleus accumbens on spatial learning and extinction in the rat.

Rats with ibotenic acid lesions of the nucleus accumbens (N. Acc) were studied in two spatial learning paradigms: a T-maze and a Morris water maze. Learning of a spatial discrimination task and its reversal in the T-maze were disrupted by the N. Acc lesions. As both original and reversal learning were impaired, there was no evidence of a specific lesion effect on reversal learning. The lesioned rats did not perseverate excessively in their choice of the previously reinforced arm. There was evidence of behavioural inflexibility during extinction when the lesioned rats failed to slow the pace at which they ran the maze in the absence of reward. Spontaneous alternation was not significantly affected by the lesion. Acquisition of the second spatial task, locating the hidden platform in the Morris water maze, was also impaired. The lesioned rats did eventually learn the task and successfully reached the platform with similar latencies and heading errors to controls. Thus, the N. Acc lesion impaired but did not abolish spatial learning in the T-maze and the water maze. The deficits observed in this study may reflect a role for the N. Acc in the reorganisation of behaviour in response to external change.

Animals↗
PubMed2002

Ethanol impairs behavioral strategy use in naive rats but does not prevent spatial learning in the water maze in pretrained rats.

RATIONALE: Ethanol impairs performance in the water maze in rats. A detailed behavioral analysis is required to fully evaluate the nature of the impairment. OBJECTIVES: A detailed behavioral analysis was carried out to evaluate the effect of ethanol on performance in the water maze task in male hooded rats given 2.0 or 6.0 g/kg ethanol by gavage. Multiple measures of water maze strategies learning and spatial learning were studied. METHODS: Water maze trials were recorded on videotape and digitized for offline analysis. Some rats were naive at the start of spatial training, whereas other rats received water maze strategies pretraining prior to spatial training to familiarize them with the general behavioral strategies required in the task. RESULTS: Naive ethanol-treated rats exhibited both spatial learning and water maze behavioral strategies impairments. There was no evidence of a spatial learning impairment that was independent of an associated behavioral strategies impairment. Further, ethanol impaired the ability of naive rats to swim to a stable visible platform. Pretrained ethanol-treated rats performed significantly better than naive ethanol-treated rats on almost all measures, and were indistinguishable from controls on most measures. CONCLUSIONS: These results suggest that ethanol may impair water maze performance in naive rats by interfering with their ability to acquire and use required water maze behavioral strategies and generate adaptive swim paths. Ethanol does not prevent robust spatial learning in rats that are familiar with required water maze behavioral strategies.

Animals↗
PubMed1984

The influence of persistent crowding on the age changes of behavioral parameters and survival characteristics of rats.

One hundred fifty-six male Sprague-Dawley rats were submitted to crowding (12 rats/Makrolon-IV cage) from an age of 5 months onwards. An equal number from the same age cohort served as a control (6 rats/Makrolon-IV cage). As part of an age-test program, behavioral parameters (spontaneous motor activity, reactive motor activity and maze-learning ability) were measured at various ages between 8 and 30 months. The rats were sacrificed for additional measurements after the behavioral tests. Survival curves and age-specific mortality rates were calculated for those rats which died spontaneously in the course of the study. Control rats showed a significant decrease in spontaneous motor activity after an age of 18 months. Reactive motor activity of the controls revealed a fall in the number of large movements between 9 and 15 months, whereas the number of small movements increased up to an age of 30 months. Crowding conditions increased significantly both spontaneous and reactive activity. Maze-learning ability declined significantly with age in the controls whereas crowded rats revealed a tendency to better performance which seemed to be submitted to a seasonal rhythm. Crowded rats showed an improved survival characteristic, beginning at an age of 700 days. Mortality curves turned out to be distinct and parallel by straight line regression. It has been concluded that the positive effects of crowding on behavioral parameters and survival could be attributed to a decrease in vulnerability rather than to a lowered rate of aging.

Aging↗
PubMed1978

The relationship of gestational age to vitamin A induced postnatal dysfunction.

In an effort to determine the relationship between time of administration and consequent behavioral effects on progeny, a uniform subteratogenic dose of vitamin A (80,000 I.U./KG) was administered to gravid Sprague-Dawley rats during one of five periods of gestation (days 5-7, 8-10, 11-13, 14-16 and 17-19). Offspring were examined for changes in rate of weight gain, locomotor activity and maze learning ability (T-maze with return to nest as reward and multiple T water maze escape). Vitamin A 8-10 animals were hyperactive, vitamin A 11-13 animals acquired T-maze slower than controls and both vitamin A 8-10 and 11-13 acquired water maze slower than controls. Vitamin A 11-13 animals were significnatly lighter than controls and all other vitamin A groups.

Animals↗
PubMed1981

Evidence for auditory localization ability in the turtle.

Evidence is presented that the semiaquatic turtle Chrysemys scripta and the terrestrial turtle Terrapene carolina major can detect the direction of a tone within their sensitive area of hearing. It is further suggested that not only can these species respond behaviorally to sound without extensive manipulation but can use limited hearing in a problem-solving situation of maze learning. Adult emydid turtles (5 C. scripta, 3 T. carolina) learned a Y-maze with a 500-c/s signal to an invisible open goal box to avoid bright light. All animals performed above chance levels, but it required over 240 trials on the average to reach 60%-correct performance. Computations suggest that binaural cues used by mammals would not be adequately encoded by the primitive auditory systems of the species studied. It is further suggested that these turtles use bone conduction by coupling their ears to the substrate to hear vibrations in the immediate area. This would appear to be a carryover from the ancient reptile stem stock. The poor middle-ear impedance system relegates air-borne sound processing to be a somewhat insensitive limited low-pass system, depending heavily on monaural cues derived from head scanning. vocal output in these species appears to be spectrally imbalanced with their auditory sensitivity. The role of species-specific vocal signalling is unclear from the present data.

Animals↗
PubMed1992

Muscimol infused into the medial septal area impairs long-term memory but not short-term memory in inhibitory avoidance, water maze place learning and rewarded alternation tasks.

These experiments investigated the effects of injections of muscimol (1 or 5 nmol), administered into the medial septal area prior to training, on memory tested at different retention delays after training in 3 tasks: an inhibitory avoidance task, a one-trial place learning task, and a rewarded alternation task. In all 3 tasks, intraseptal injections of muscimol did not impair memory performance at short retention delays, but impaired memory at the longer retention delays. These findings are consistent with the view that GABAergic regulation of the septohippocampal cholinergic system plays a selective role in the establishment of long-term memory.

Animals↗
PubMed1991

A water-maze discrimination learning deficit in the rat following lesion of the habenula.

Although the habenula occupies a potentially important link between forebrain and midbrain, lesion of the complex produces little effect in most standard behavioral paradigms. More recently, it has been shown that such lesions may impair the ability to initiate or switch responses appropriate to environmental contingencies but only under demanding conditions. Although such deficits have been described as response failures, they could equally well be attributed to restricted attentional mechanisms. The present study was designed to further substantiate a role for the habenula in acquisition of adaptive behavior under demanding conditions and to examine the possible contribution of attentional failure. The initial response preference to 'escape' onto platforms situated in two chambers at the distal end of a water tank was established for groups of lesioned and sham-operated rats. Rats were subsequently trained in discrete trials to escape by choosing the side of the nonpreferred chamber. During training the choice of escape chamber was cued by distracting black or white visual stimuli displayed on the tank sides and above the entrances to the chamber. These were moved over trials so as to be nonpredictive of the appropriate escape position. Lesioned animals were significantly impaired in the acquisition of this positional discrimination. Analysis of response times suggested that both lesion and control animals were attending to the irrelevant visual cue. The results confirm a behavioral inflexibility following lesion of the habenula and suggest that this deficit cannot be explained simply in terms of a failure to attend to environmental cues. The lesion deficit also could not be attributed to a response perseveration.

Animals↗
PubMed1987

Pure topographical disorientation: a definition and anatomical basis.

Four patients showing the syndrome of "topographical disorientation" are reported. Patients became unable to find their way, especially in unfamiliar surroundings, following a single lesion in the territory of the right posterior cerebral artery, as evidenced on CT-scan. Associated disturbances included: left hemianopia, mild face recognition problems, and various degree of impairment in face-learning and visual maze-learning tasks. Language, visuo-perceptive and constructional abilities, object and picture recognition were intact. Memory tests only showed a mild, generally non-significant, impairment of visual memory. As inferred from the lesion located in the 4 patients, this syndrome seems to be strongly related to damage to the right parahippocampal gyrus, a structure that thus appears crucial for specifically storing and/or retrieving visual information necessary to achieve orientation in the locomotor environment.

Adult↗
PubMed1991

Molecular mechanisms of memory and drug dependence.

Addiction has long been thought to include both metabolic and psychological dependence. Psychological dependence must involve long-term memory of behavioral patterns in response to specific experimental contexts. Mammalian memory, and more specifically, human memory, is largely associative. Animal models of associative memory have been provided by Pavlovian conditioning of the snail Hermissenda crassicornis and the rabbit. Striking parallels have been observed in the intrinsic molecular and biophysical transformations which accompany acquisition of the conditioned response in these different animals. In brief, associated stimuli cause elevation of Ca2+ and diacylglycerol, translocation of protein kinase C, phosphorylation of a membrane-associated G-protein, reduction of K+ currents, modification of axonal transport and structural alterations of neuronal branches. These changes can be understood and modelled as a plausible basis for memory acquisition during conditioning as well as more cognitively relevant learning such as spatial maze learning for which related neuronal alterations have recently been found. Identification of memory-specific molecular steps may help target pharmacologic agents for amelioration of learned aspects of psychiatric syndromes such as those of drug dependence.

Animals↗
PubMed2005

A new mathematical model for assessment of memorization dynamics.

A new memory model is proposed based on regression analysis and exponential- shaped learning curves. The efficacy of the model is tested with several types of experiments including food aversion in snails, maze learning in rats and memory tests for adults and children. The model is also tested on drug abusers and alcoholics. The results of goodness of fit tests indicate that our model can accurately be used to predict the memory dynamics of diverse experiments and populations. The model can also be used to predict both group and individual performance. The application of the model to detect memory impairment is discussed, as are limitations.

Adult↗
PubMed2005

Subordinate male mice show long-lasting differences in spatial learning that persist when housed alone.

In the wild, house mice live in social groups, whereas in the laboratory male mice are often singly housed. Environmental enrichment such as that provided by social housing has been argued to improve the cognitive performance of laboratory animals in experimental tests. The aim of the present study was to test the cost of aggressive social interactions on learning in male CD-1 mice. We found that subordinate mice from more aggressive dyads showed spatial learning impairment, measured as alternation on a T-maze. Learning impairments in subordinates have hitherto been presumed attributable to the animals' exposure to, and relative standing within, the social group. By contrast, the impairment we observed could not have been the result of recent social defeat because it persisted weeks later when the mice were housed alone. Elevated urinary corticosterone predicted later subordination, though paradoxically these abnormally high levels were reduced by pair housing.

Analysis of Variance↗