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PubMed1991

Social feeding reverses learned flavor aversions in spotted hyenas (Crocuta crocuta).

Spotted hyenas are highly social carnivores with competitive feeding habits. It was hypothesized that social feeding might be capable of reversing an established flavor aversion. The dominant hyena of each of 4 captive social groups was given a novel food mixed with LiCl on Day 1; aversion to this food was demonstrated on Day 2. On Day 3, the dominant hyena and 3 or 4 members of her group were offered the food simultaneously. Three of the 4 dominant hyenas ate substantial quantities of the food during this group feeding, and all 4 hyenas ate the following day when offered the food alone. In contrast, when averted to a different novel food, the hyenas refused that food on 3 consecutive days. In this species social factors, such as those operating during group feeding, are sufficiently powerful to attenuate, immediately and dramatically, a strong LiCl-induced aversion.

Animals↗
PubMed1988

Maturational influences on perseveration of avoidance and reversal learning after selected brain damage in rats.

In Experiment I, 18 weanling and 18 adult male rats received bilateral electrolytic lesions of the dorsomedial or ventrolateral prefrontal cortex, or the hippocampus, while 12 additional pups and adults served as nonoperated controls (n = 6/group). Subjects were observed for perseverative responding in acquisition of a stepup avoidance task, followed by reversal training and extinction. Thirty days later, subjects were retrained and tested in the same manner. During initial training, the numbers of trials to criteria, errors, and latencies on the last 5 trials all indicated significant effects from age, primarily, and surgery, secondarily. After 30 days, surgical effects assumed a more dominant role, with hippocampal and ventrolateral damage producing the greatest extent of response perseveration. Experiment II replicated the essential procedural sequence as Experiment I, but included damage from combined lesions. 24 weanlings and 24 adults received bilateral lesions to the dorsomedial prefrontal cortex, the dorsomedial prefrontal cortex plus caudate nucleus, or sham lesions. Subjects from this experiment were trained after 7 days or 60 days recovery (n = 6/group). The acquisition results indicated that all independent variables were significant, but only the age effect attained significance in the extinction data. Both experiments point to the profound influence of age at the time of damage in accounting for recovery of avoidance behavior.

Aging↗
PubMed2002

Multiple injections of thyrotropin releasing hormone fail to reverse learning and memory deficits in rats with lesions of the nucleus basalis of meynert.

The learning and memory enhancing effects of thyrotropin releasing hormone (TRH) was examined in an animal model of Alzheimer's disease. Adult rats were prepared with either sham surgeries or cholinergic lesions of the nucleus basalis of Meynert (nbM). Subjects were injected (ip) with one of three doses of TRH (0, 5, 10 mg/kg) starting on the day of surgery and continuing once every other day for a total of four injections. Performance (four trials/day for 4 days, 30 m inter-trial interval) in a Morris water maze was assessed one week after the last TRH injection (i.e., 2 weeks postoperatively). Latency to find the hidden platform served as the dependent variable. Results indicated that damage to the nbM impaired task performance in that animals with nbM lesions generally required more time to find the platform and showed less trial-to-trial improvement. Treatment with TRH failed to reverse this lesion-induced deficit. These results suggest that multiple injections of TRH do not provide residual protection against the deleterious effects on learning and memory produced by cholinergic lesions of the basal forebrain. Other doses and administration parameters, however, need to be studied in order to determine the generalizability of these findings.

Alzheimer Disease↗
PubMed1999

Spatial and reversal learning in congeneric lizards with different foraging strategies.

Environmental demands that require intensive search for mates, food and nest sites are correlated with efficient spatial memory in many mammalian and avian species. This convergence of evidence has led to the view that spatial memory, and the neurological structures associated with it, have been selected in niches that require memory for the location of goal objects. Whether such evolutionary demands are also correlated with nonspatial abilities that require flexible use of associations similar to those required for spatial memory has not been well studied. In addition, correlations between niche types and the use of spatial or nonspatial memory have not been investigated in nonmammalian, nonavian taxa. In this study, we investigated the relationship between foraging strategies and performance on two tasks, one spatial and the other nonspatial, in congeneric lizard species: Acanthodactylus boskianus, an active forager that collects clumped sedentary prey, Acanthodactylus scutellatus, a sit-and-wait predator that collects distributed mobile prey. The two species did not differ in their performance of a spatial memory task, but A. boskianus, the active forager, performed better on the reversal of a visual discrimination, a nonspatial task. These findings question the generality of the spatial adaptation model for vertebrates. We present the pliancy hypothesis, which we developed to account for these results. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1987

Amphetamine reverses learning deficits in 6-hydroxydopamine-treated rat pups.

At 5 days of age, rat pups were treated with a combination of desmethylimipramine (DMI) and 6-hydroxydopamine (6-OHDA) to selectively deplete brain dopamine (DA) or with vehicle (saline) control solutions. Two days later, all animals received conditioning to a novel odor by pairing the odor with intraoral milk. When the odor was anise, treated pups spent less time near the conditioned stimulus than did controls, but there were no 6-OHDA effects when the stimulus was a lemon odor (Experiment I). The difference in performance between the treated and control animals was not attributable to alterations in activating effects of the reinforcer (Experiment I), changes in olfactory sensitivity or olfactory preference (Experiment II), or sensitization to the stimulus (Experiment III). In Experiment IV, animals received d-amphetamine sulfate (0.5 mg/kg) prior to conditioning, testing, or both conditioning and testing. Amphetamine treatment before conditioning produced an improvement in performance in animals previously treated with 6-OHDA/DMI, but it impaired performance in controls, regardless of the time of injection. The results indicate a role of brain DA in learning in young rats.

Animals↗
PubMed1997

The spectrum of acquired cognitive disturbances in children with partial epilepsy and continuous spike-waves during sleep. A 4-year follow-up case study with prolonged reversible learning arrest and dysfluency.

We report a longitudinal study (7-11 years) of a previously normal boy (MR) who presented from the age of 5 years with rare partial motor seizures and atypical 'absences'. The history revealed a stagnation in development and speech difficulties a few months before onset of his epilepsy. The first waking electroencephalogram (EEG) showed rare generalized discharges during hyperventilation. Magnetic resonance imaging revealed an arachnoid cyst in the frontotemporal region. Although his epilepsy never became severe, he experienced important learning difficulties. Subsequent EEGs became increasingly active with left focal epileptic activity and continuous spike-waves during sleep (CSWS) present from the first sleep EEG. The first neuropsychological evaluation (7 years) showed a speech dysfluency, word finding and naming problems, inattention and low intelligence quotient. Carbamazepine was changed to clobazam and later ethosuximide was added with a rapid improvement (within 1 month) in linguistic and cognitive performances as well as in behaviour. Furthermore, the patient showed considerable progress in acquisition over the next months whereas learning to read had previously been very difficult. The epileptic activity gradually disappeared and he was able to follow regular school at an age-appropriate level. This case adds a new facet to the already recognized more obvious acquired neuropsychological disturbances known to occur in some partial childhood epilepsy syndromes with CSWS (aphasia, dementia). It manifested as prolonged insidious stagnation in learning and subtle language disability. This study documents rapid specific language improvement with change in anti-epileptic drugs and a restored immediate and long-term learning capacity, suggesting a direct but 'hidden' role of epilepsy.

Anticonvulsants↗
PubMed2004

Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats.

Cognitive impairment is common after ischemic stroke. In rodent stroke models using occlusion of the middle cerebral artery (MCA) this is reflected by impaired spatial memory associated with the size of the ischemic lesion. Housing in an enriched environment enhances brain plasticity and improves recovery of sensorimotor functions after experimental stroke in rats. In this study we report that postischemic housing in an enriched environment also attenuates the long-term spatial memory impairment after MCA occlusion and extinguishes the association between spatial memory and infarct volume. An enriched environment did not significantly alter the expression of selected neuronal plasticity-associated genes 1 month after MCA occlusion, indicating that most of the adaptive changes induced by an enriched environment have already occurred at this time point. We conclude that the attenuated memory impairment induced by environmental enrichment after MCA occlusion provides a useful model for further studies on the neurobiological mechanisms of recovery of cognitive functions after ischemic stroke.

Animals↗
PubMed2006

Visuomotor learning in immersive 3D virtual reality in Parkinson's disease and in aging.

Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls in adapting to the horizontal component of the biaxial discordance. More importantly, when the biaxial discordance was reversed, PD patients were unable to make appropriate movement corrections. Therefore, they showed significantly degraded learning indices relative to age-matched controls for both dimensions of the biaxial discordance. Together, these results suggest that the ability to adapt to a sudden biaxial visuomotor discordance applied in three-dimensional space declines in normal aging and Parkinson disease. Furthermore, the presence of learning rate differences in the PD patients relative to age-matched controls supports an important contribution of basal ganglia-related circuits in learning novel visuomotor coordinations, particularly those in which subjects must learn to adapt to sensorimotor contingencies that were reversed from those just learned.

Adaptation, Physiological↗
PubMed1994

Diazepam impairs place learning in native but not in maze-experienced rats in the Morris water maze.

Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.

Animals↗
PubMed2003

Evaluation of the effect of chronic administration of drugs on rat behavior in the water maze task.

Tissue accumulation of intermediates of the metabolism occurs in various inherited neurodegenerative disorders, including methylmalonic acidemia (MA). Animal cognition is usually tested by measuring learning/memory of rats in behavioral tasks. A procedure in which rats are chronically injected with the metabolites accumulating in the neurometabolic disorder methylmalonic acidemia from the 5th to the 28th day of life is described. The animals were allowed to recover for approximately 30 days, after which they were submitted to the Morris water maze task. This behavioral task consisted of two steps. The first one is called the acquisition phase, where rats were trained for 5 consecutive days performing four trials per day to find the submerged platform. On each trial, the rat was placed in the water in one of four start locations (N, S, W and E). The animal was then allowed to search for the platform for 60 s. Once the rat located the platform, it was permitted to remain on it for 10 s. The acquisition phase was followed by the probe trial 24 h later, in which the platform is not present. The time spent in the quadrant of the former platform position and the correct annulus crossings were obtained as a measure for spatial memory. The next step was the reversal learning (reversal phase) performed 2 weeks later. Animals were trained for 4 days (four trials per day) to find the hidden platform, which had now been moved to a position diagonally opposite (reversed) from its location in the acquisition phase. On the next day, all animals were submitted to a second probe trial, similar to the first one. We observed that rats chronically injected with methylmalonic acid (MA), although presenting no alterations in the acquisition phase, showed a long lasting reversal learning impairment. Moreover, motor activity, evaluated by the swim speed in the maze, was not altered by MA administration. These results are consistent with perseverative behavior.

Animals↗
PubMed1996

Effects of social isolation rearing on learning in the Morris water maze.

Impaired learning has been shown as a consequence of isolation-rearing in a variety of paradigms. However, there are situations in which learning in isolation-reared rats is enhanced or unimpaired compared to socially reared rats. The present experiments investigated the effects of isolation rearing on place navigation in the Morris water maze. Two complementary paradigms were studied: isolation and socially reared rats were exposed to the water maze either without drug pretreatment or following systemic administration of scopolamine. Two conditions were examined: place learning and reversal learning. Male Lister hooded rats were either housed singly (isolation reared) or in groups of four (social reared) from weaning at 21 days of age. Six weeks later place learning and reversal learning were determined using the Morris water maze. The time taken to locate the submerged island (escape latency) was used as the measure of learning ability. The results showed that place learning, and reversal learning were enhanced in isolation reared rats compared to socially reared controls. Pretreatment with scopolamine (0.3 and 0.5 mg/kg, i.p.) produced a dose-related cognitive deficit as shown by an increase in the escape latency. Scopolamine (0.3 mg/kg) impaired both place and reversal learning but this was less pronounced in isolation compared to socially-reared rats. These results suggest that rearing in isolation may enhance spatial learning though central cholinergic mechanisms.

Animals↗
PubMed2003

Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial.

RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. METHODS: Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. RESULTS: There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex.

Aged↗
PubMed1996

Age-dependent spatial memory deficits in transgenic mice expressing the human mid-sized neurofilament gene: I.

Previous studies have revealed that the transgenic mouse line expressing the human neurofilament-mid-sized (NF-M) gene evidences age-dependent and cell-specific pathological neurofibrillary accumulation in the central nerve system. In the current study, we investigated the learning and memory processes of NF-M transgenic mice at 3 and 8 months of age in a modified Morris water maze using a series of tasks including those primarily related to reference memory (i.e., spatial learning, reversal learning and probe trials) and to working memory (i.e., matching to sample tasks with or without delays). At 3 months of age, NF-M transgenic mice were indistinguishable from age- and litter-matched non-transgenic wild-type controls on any of the tests of reference and working memory. At 8 months of age, however, the NF-M transgenic mice exhibited significantly poorer performance than the age- and litter-matched wild-type control mice on both reference and working memory tasks. Immunohistological study of the brains of the 8-month-old NF-M transgenic mice revealed spherical and tangle-like neurofilamentous accumulation in their cerebral cortices. These results suggest that NF-M transgenic mice express both age-related histopathological changes and age-dependent learning and memory deficits. Whether NF-M transgenic mice exhibit even more severe behavioral impairments when they become aged is currently under study.

Aging↗
PubMed1999

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats.

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.

Animals↗
PubMed2006

Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism.

Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 and tested their offspring from Postnatal Day (PND26-31) on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children . This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder.

Analysis of Variance↗