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The acquisition, retention and reversal of spatial learning in the morris water maze task following withdrawal from an escalating dosage schedule of amphetamine in wistar rats.

Two experiments were carried out to evaluate the effects of amphetamine withdrawal in rats on spatial learning in the water maze. A schedule of repeated d-amphetamine administration lasting for 6 days, with three injections per day (1-5 mg/kg, i.p.), was employed. Experiment 1 demonstrated that amphetamine withdrawal did not impair the acquisition of the water maze task (third to fourth withdrawal days), but amphetamine-withdrawn rats made more target-zone visits and reached the former location of the platform quicker than controls during the probe test (fifth withdrawal day). In experiment 2, retention of the location of the escape platform was assessed in animals having been pre-trained on the water maze task before treatment. On the third withdrawal day, retention of the former platform location was assessed in a probe test. Retention was only clearly seen in the measure of target zone visits, and performance did not differ between groups. Next, the animals were trained to escape to a new location in the water maze on withdrawal days 4-5. A reversal effect could be discerned across the first four trials, as evident by the animals' tendency to search in the former target quadrant. This interfered with the new learning, but amphetamine-withdrawn animals appeared to overcome it more rapidly than saline-treated controls. This finding is consistent with the view that amphetamine withdrawal can enhance behavioural switching, which could be expressed as a reduction of proactive interference during learning; and, it is in line with our previous finding that latent inhibition is also attenuated during amphetamine withdrawal.

Amphetamine↗

Vasopressin potentiation in the performance of a learned appetitive task: reversal by a pressor antagonist analog of vasopressin.

Rats were tested in a simple one-trial water-finding task for the effects of arginine vasopressin (AVP) on performance of an appetitive task. On the training day, each animal was exposed for 5 min to a novel open-field environment that contained a water-tube located in an alcove set into one of the walls of the enclosure. Immediately upon removal from the enclosure, the animals received a subcutaneous injection of either AVP (1 microgram/rat) or vehicle solution. When water-deprived and tested 48 hr later, vasopressin-treated rats found the water tube reliably faster than controls. In other groups of animals, this potentiation in learned performance was prevented by concurrently treating the rats with a vasopressin analog having potent pressor antagonist properties. These results are consistent with the notion that vasopressin may play a role in memory consolidation, but peripheral visceral factors may mediate this action.

Animals↗

Effect of postweaning nutritional and environmental restrictions on discrimination learning in albino rats.

Charles Foster littermate albino rats (72) were randomized into 9 independent groups in a 3 x 3 factorial design by varying nutrition and environment each at three levels: normal nutrition, 25% nutritional restriction and 50% nutritional restriction; normal environment, 3-week environmental restriction and 6-week environmental restriction. The nutritional and environmental restrictions were imposed from the 30th day of life for 6 weeks. The animals were subsequently tested for black/white original learning followed by reversal discrimination learning in a T-maze. The results indicated significant main effects for nutrition and environment on indices of learning ability. However, the nutrition x environment interaction was not significant. Post hoc analysis revealed that moderate and severe nutritional restriction as well as long-term environmental restriction caused significant discrimination learning deficits. Short-term environmental restriction failed to produce significant effect on learning behaviour. The results are discussed in context of environmental stress effects, altered brain mechanisms and psychological changes such as increased drive level and emotionality of the animal.

Animal Nutritional Physiological Phenomena↗

Reversibility of manganese-induced learning defect in rats.

In this study the mechanism by which manganese (Mn) induces learning defect and its reversibility has been investigated in rats. Female albino rats were dosed orally with 357 micrograms Mn/kg body weight for 15 or 30 days. Attempts were made to correct the Mn-induced learning defect by (1) co-administration of mevinolin and Mn for 30 days; (2) administration of mevinolin for 15 days after 15 days of dosing with Mn, and (3) by withdrawal of Mn treatment (15 days dosing with Mn followed by 15 days without Mn). Mevinolin was given orally at 235.7 micrograms/kg body weight. Significant increases in the Mn and cholesterol levels in the hippocampus were accompanied by an obvious slowness in learning of rats exposed to Mn. After one training period (day 29) the time required to reach the exit of a T-maze was 104.5 +/- 13.8 sec for rats dosed with Mn for 30 days, whereas that of the controls was 28.7 +/- 11.4 sec on day 30. This delay was completely corrected (to 30.7 +/- 6.0 sec) in rats co-administered mevinolin (an inhibitor of cholesterol biosynthesis) with Mn. Withdrawal of Mn, with or without inhibiting the cholesterol biosynthesis, also corrected the Mn-induced learning defect. These results suggest that Mn toxicity produces learning disability by increasing cholesterol biosynthesis and this reversible disability in learning can be corrected by withdrawal of Mn exposure.

Administration, Oral↗

Learning to see the trees before the forest: reversible deactivation of the superior colliculus during learning of local and global visual features.

Previous studies have established that deactivation of the superior colliculus severely retards the normally rapid learning of pattern discriminations in the mature cat. The purpose of this study was to test the hypothesis that the midbrain plays an important role in the learning of simple pattern discriminations and that the contribution of this pathway is to the perception of global, rather than local, features of a figure. To answer this question, pattern discrimination learning was studied in three intact cats and in three experimental cats during bilateral reversible deactivation of the superficial layers of the superior colliculus (SC). The animals concurrently learned to discriminate three pairs of compound visual patterns composed of small (local element) Ts or 7s. Congruent and incongruent stimulus pairs were large (global) Ts vs. 7s comprising the same or different local elements, respectively. The random stimulus pair consisted of randomly scattered local elements (Ts vs. 7s). The animals were trained to respond to the large Ts in the congruent and incongruent pairs and the small Ts in the random pair. In the normal cats, learning of the random pair was much slower than the learning of the congruent and incongruent pairs. This finding demonstrated the theory of global precedence, because the animals learned the global features of the congruent and incongruent pairs much more quickly than the local features of the random pair. In contrast, during bilateral deactivation of the superficial layers of the SC, the learning of the incongruent pair was significantly retarded and took longer to learn than the random pair. Congruent and random pair learning rates were unchanged. The specific deficit in learning the incongruent pair indicates that the learning of global, but not local, elements of the visual pattern is impaired during deactivation of the SC. The unimpaired use of local features permitted the animals to learn the congruent and random pairs at normal rates. Therefore, deactivation of the superficial layers of the SC during pattern discrimination learning reverses the precedence for global visual features that is typical of normal learning.

Animals↗

Forced use of hemiplegic upper extremities to reverse the effect of learned nonuse among chronic stroke and head-injured patients.

To test the clinical counterpart of the learned nonuse theory, 25 chronic hemiplegic stroke and head-injured patients with minimal to moderate upper extremity extensor muscle function were required to keep their uninvolved upper extremities within a hand-enclosed sling during waking hours over a 2-week interval. During this forced use period and for 1 year thereafter, changes in force or time-based measures among 21 functional tasks were compared to values at the sixth baseline session, a preintervention time when relearning had plateaued. Significant (P less than 0.05, Friedman's repeated measures followed by Tukey multiple comparison tests) changes were seen in 19 of the 21 tasks with most persisting at the 1-year follow-up. There were no apparent differences between right- and left-sided involvement or between stroke versus head injury clients (Mann-Whitney procedure). Ratings for quality of movement scored from videotapes presented in random order showed no change over time. These data suggest that learned nonuse does occur in select neurological patients and that this behavior can be reversed through application of a forced use paradigm.

Adult↗

"Reminiscence" in the cold flour beetle (Tenebrio molitor).

Retention of a T-maze task by adults of the species Tenebrio molitor was facilitated by exposure to 1.7 degrees C. The facilitation effect was seen after 1, 3, 4, or 5 days of retention, but is was reversed after 2 days. The increment from day 2 to day 5 was termed "reminiscence." That these effects represented alterations in memory and not nonspecific motivational factors was determined by requiring another group of beetles to reverse their learning of the original task. Since reversal performance was inversely related to relearning, it was concluded that "reminiscence" represented alterations in memory. A multistage memory mechanism in the beetle was postulated.

Animals↗

The functions of the orbitofrontal cortex.

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as taste) is reversed. This is an example of stimulus-reinforcement association learning, and is a type of stimulus-stimulus association learning. More generally, the stimulus might be a visual or olfactory stimulus, and the primary (unlearned) positive or negative reinforcer a taste or touch. A somatosensory input is revealed by neurons that respond to the texture of food in the mouth, including a population that responds to the mouth feel of fat. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex can impair the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when there are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face (and voice) expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion. The approach described here is aimed at providing a fundamental understanding of how the orbitofrontal cortex actually functions, and thus in how it is involved in motivational behavior such as feeding and drinking, in emotional behavior, and in social behavior.

Animals↗

Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome.

Mice with segmental trisomy of chromosome 16 (Ts65Dn) have been used as a model for Down's syndrome. These mice are born with a normal density of basal forebrain cholinergic neurons but, like patients with Down's syndrome, undergo a significant deterioration of these neurons later in life. The time course for this degeneration of cholinergic neurons has not been studied, nor is it known if it correlates with the progressive memory and learning deficits described. Ts65Dn mice that were 4, 6, 8, and 10 months old were sacrificed for evaluation of basal forebrain morphology. Separate groups of mice were tested on visual or spatial discrimination learning and reversal. We found no alterations in cholinergic markers in 4-month-old Ts65Dn mice, but thereafter a progressive decline in density of cholinergic neurons, as well as significant shrinkage of cell body size, was seen. A parallel loss of staining for the high-affinity nerve growth factor receptor, trkA, was observed at all time points, suggesting a biological mechanism for the cell loss involving this growth factor. Other than transient difficulty in learning the task requirements, there was no impairment of trisomic mice on visual discrimination learning and reversal, whereas spatial learning and reversal showed significant deficits, particularly in the mice over 6 months of age. Thus, the loss of ChAT-immunoreactive neurons in the basal forebrain was coupled with simultaneous deficits in behavioral flexibility on a spatial task occurring for the first time around 6 months of age. These findings suggest that the loss of cholinergic function and the simultaneous decrease in trkA immunoreactivity in basal forebrain may directly correlate with cognitive impairment in the Ts65Dn mouse

Animals↗