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Learning and memory in agmatine-treated rats.

Agmatine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, was examined for its role in water maze place learning, contextual and auditory-cued (discrete) fear learning and conditioned taste aversion learning, when administered systemically. Male Wistar rats were given saline or 1, 5, 10 or 50 mg/kg agmatine ip 20 min prior to or 30 min following daily training sessions in a hidden-platform (place learning) water maze task. Agmatine did not affect latencies to find the hidden platform or preference for the training quadrant during probe trials. When administered 20 min prior to contextual or auditory-cued fear-conditioning sessions, these doses of agmatine evoked a linear dose-dependent impairment in the magnitude of learned fear to the contextual stimuli when assessed during extinction trials 24 h later, but had no effect on the magnitude of learned fear to the auditory stimulus. Inferences of baseline motor activity and ability to respond to the presentation of footshock stimuli were not affected by the treatment. Injections of 50 mg/kg agmatine concurrently with a malaise-evoking agent following presentations to a novel sucrose solution abolished learned taste aversions; this agent did not evoke conditioned taste aversions alone. These studies indicate that systemically administered agmatine selectively impairs behavioral inferences of specific types of learning and memory.

Agmatine↗

Physiological, pathophysiological and therapeutic roles of 5-HT systems in learning and memory.

Multiple 5-hydroxytryptamine (5-HT) receptors have been identified (5-HT1A/1B/1D/1E/1F, 5-HT2A/2B/2C, 5-HT3A/3B, 5-HT4A/4B, 5-HT5A/5B, 5-HT6 and 5-HT7A/7B/7C/7D) and extensive evidence suggests that 5-HT receptors have a role in learning and memory. Indeed, available evidence strongly supports physiological, pathophysiological and therapeutic roles of 5-HT systems in cognitive processes, although the evidence seems incomplete. Indeed, there has been a clear tendency to use pre-learning administration most frequently, whereas post-learning and pre-retention administration protocols have been utilized in only a few studies, and probably this trend has led to missed relevant information. For instance, when pre- vs post-training administration of 5-HT1A agonist, 5-HT2 antagonists and 5-HT4 agonists have been compared contrasting findings were reported in aversive and appetitive learning tasks. Emerging evidence also indicates that 5-HT1A and 5-HT4 receptor agonists, as well as, 5-HT1A antagonists, 5-HT2 antagonists, 5-HT3 antagonists and 5-HT uptake inhibitors may have therapeutic utility in the treatment of Alzheimer's disease and amnesia. Inasmuch as the activation or blockade of diverse 5-HT receptors is able to modulate cognitive processes, and 5-HT uptake inhibition could have therapeutic applications in the treatment of cognitive disorders, it seems evident that the role of 5-HT in learning and memory is more complex than a simple imbalance. Consequently, the notion that activation of the 5-HT systems impairs performance, whereas reduced serotonergic function may facilitate learning, must be reconsidered.

Animals↗

Age-dependent effects of hippocampal muscarinic receptor blockade on memory-based learning in the developing rat.

The effects of ventral intrahippocampal injections of atropine sulfate on patterned single alternation (PSA), a discrimination task that requires intact short-to-intermediate-term memory, were examined in the developing rat at 16-17 and 28-32 days of age. Atropine treatment disrupted simple acquisition in some 16- to 17-day-old pups by interfering with approach to the goal, but did not eliminate PSA at either 8- or 15-s intertrial intervals when approach was normal. In the older rats, atropine treatment delayed the onset and reduced the magnitude of PSA, indicating a reduced memory-based discrimination. These results provide additional support for an increasing role of muscarinic receptors in learning and memory as this system matures in the developing rat, and suggest different mechanisms for PSA at the two ages.

Aging↗

Executive function, memory, and learning in Tourette's syndrome.

Young people with Tourette's syndrome (TS) alone, TS plus attention-deficit/hyperactivity disorder (+ADHD), or TS plus obsessive-compulsive disorder (+OCD) were compared with a healthy control group on a set of measures of executive functioning, memory, and learning. The TS-alone group was impaired on one executive measure involving inhibition and strategy generation but did not differ significantly from the healthy control group on other measures. The TS+ADHD group showed impairment on several executive measures. There was no evidence of impairment in implicit aspects of memory and learning for any of the TS groups. The findings are discussed in terms of the frontostriatal hypothesis of TS and the contribution of comorbid symptomatology.

Adolescent↗

Working memory in learning disability subgroups.

The purpose of this study was to investigate (a) the degree to which working memory differences between learning-disabled and nondisabled children reflect a specific or generalized deficit, and (b) whether limitations in the enhancement of learning-disabled student's working memory performance are attributable to process or storage functions. To this end, performances of reading-disabled, math-disabled, chronological age (CA)-matched, and achievement-matched children were compared on verbal and visual-spatial working memory measures under initial, gain, and maintenance conditions. The results indicated that: (a) learning-disabled subtypes were not differentiated by their performance on verbal and visual-spatial working memory measures; and (b) learning-disabled children's working memory performance was inferior to CA-matched and superior to achievement-matched counterparts across initial, gain, and maintenance conditions. The results suggest that learning-disabled children suffer generalized working memory deficits, possibly due to storage constraints in the executive system.

Attention↗

Age-related changes in learning and memory and cholinergic neuronal function in senescence accelerated mice (SAM).

The senescence-accelerated mouse (SAM) has been established as a murine model of accelerated aging. We investigated learning ability and memory in various tasks in a SAM strain, SAMP1TA, and in a control strain of SAMR1TA at the ages of 20, 30 and 40 weeks. We also measured choline acetyltransferase (ChAT) and cholinesterase (ChE) activity in the brains of these mice at the same ages. In a Y-maze task, in which short-term memory can be examined, there was no difference in learning ability between SAMP1TA and SAMR1TA at any age. Ability in latent learning and passive-avoidance tasks was less in SAMP1TA at 30 weeks of age than in age-matched SAMR1TA. The level of ChAT activity in the striatum of SAMP1TA was lower, than that of SAMR1TA at the ages of 20 and 30 weeks. At the ages of 40 and 50 weeks, ChE activity in the striatum of SAMP1TA was lower than that of SAMR1TA. These results suggest that SAMP1TA has a deficit, with cholinergic neuronal dysfunction, in learning ability and memory, as shown by impairment of performance in latent learning and long-term memory, but not in short-term memory.

Aging↗

Neuropsychological function in schizophrenia. Selective impairment in memory and learning.

Unmedicated schizophrenic patients (according to DSM-III-R criteria) (n = 36) and age-matched normal controls (n = 36), balanced for parental socioeconomic status, were administered a battery of standardized neuropsychological tests. Patients showed generalized impairment relative to controls and a selective deficit in memory and learning compared with other functions. Selective impairment was not found on tests related to frontal system function (abstraction, verbal fluency, and motor). The observed pattern is consistent with greater involvement of the temporal-hippocampal system, against the background of diffuse dysfunction. Although impairment in memory and learning has been reported, the selectivity and relative severity compared with other behavioral functions have not been recognized. The specificity of this profile merits further examination. These findings lend support to the hypothesized importance of the temporal-hippocampal region in understanding the pathophysiology of schizophrenia.

Adult↗

Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.

Aged↗

Learning and memory for hierarchical relationships in the monkey: effects of aging.

Young and aged rhesus monkeys were tested on 2 versions of a transitive inference task measuring learning and memory for hierarchical relationships. Animals initially acquired 4 object discrimination problems arranged such that the relationship between the stimuli followed the hierarchy A > B > C > D > E. The second version of the task was similar but involved a series of 7 objects. Learning and memory for the hierarchical relationships were evaluated during probe trials in which novel pairs of nonadjacent items (e.g., B and D) were presented for a response. Standard task accuracy measures failed to distinguish young and aged subjects at any point in training. In contrast, response latency effects that are indicative of relational information processing in young monkeys were entirely absent in aged subjects. The findings highlight the value of a relational memory framework for establishing a detailed neuropsychological account of cognitive aging in the monkey.

Aging↗

Procaine impairs learning and memory consolidation in the honeybee.

In vertebrates local anaesthetics lead to various learning deficits, depending on the site and time of injection. In this study we show the effects of the local anaesthetic procaine on learning and memory in an invertebrate, the honeybee. Reversible blocking of neuronal processes leads to different memory deficits depending on the time window during which the local anaesthesia is in effect.

Anesthetics, Local↗