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The effect of altered selenium and vitamin E nutritional status on learning and memory of third-generation rats.

It has been proposed that selenium (Se) and Vitamin E (Vit E) are involved synergistically in protection of cell membrane lipids from peroxidation. However, little is known about the effect of both deficiencies of Se and Vit E and toxic status of those antioxidants on the peroxidation potentiality of the brain. We aimed to study the effects of both Se and Vit E inadequate diet and Se rich diet on the learning and memory processes of third-generation young rats. Their ancestors were also fed by the same diets starting from their births. To test the learning and memory, the rats aged 60 days were trained by using automated two ways active avoidance shuttle box. The acquisition tests were terminated with training the rat from each group to be 25 trials per day during three days. Ten days after the last acquisition test, the retention test was performed and the acquisition of the conditioned avoidance responses (CAR) of the rats were evaluated. It is demonstrated that the CAR of all rats from three groups showed a significant increase in three consecutive days while the differences observed in CAR of same sessions was not significantly different among three groups. The memory process of these young rats also was not affected significantly by two types of diets. Under the light of our results one can suggest that, in the case of alterations in antioxidant defense status, the learning and the memory mechanisms seems to be not affected. Further researches are needed to be able to explain the possible role of oxidative stress on the mechanisms of learning and memory.

Animals↗

(+)-Eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a putative cognitive enhancer, facilitates recovery from concussive brain injury-induced learning and memory impairments in mice.

We characterized alterations in the ability of concussive brain injury (CBI) models to perform a water-finding task and examined effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel apovincaminic acid derivative, on post-traumatic impairments in latent learning and memory processes. Two types of CBI-induced amnesia (retrograde and anterograde) were produced by means of post- or preacquisition head impact using a simple weight-drop device. Profound impairments of latent learning and memory processes related to retention and retrieval were observed in the CBI mice. In the CBI-induced retrograde amnesia model, VA-045 (0.5-4.0 mg/kg) significantly ameliorated impairments of latent learning and retention in both the retention test and the retest. In the CBI-induced anterograde amnesia model, the protective effects of the compound on impairments in latent learning and retention or retrieval were significant in both the retention test and the retest. These results suggested that VA-045 may be a novel cognitive enhancer for attenuating or protecting against the learning and memory dysfunction associated with CBI.

Amnesia, Retrograde↗

Nitric oxide in learning and memory.

The role of nitric oxide in the central nervous system is described. The main part of this article concerns the problem of learning and memory.

Adaptation, Physiological↗

Pharmacological characterization of the ameliorating effect on learning and memory impairment and antinociceptive effect of KT-95 in mice.

3-Acetoxy-6beta-acetylthio-10-oxo-N-cyclopropylmethyl-dihydronormorphine (KT-95) is a synthesized compound that binds to mu-, delta- and kappa-opioid receptors in vitro. KT-95 induces analgesia and this effect is antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. We have reported that kappa-opioid receptor agonists improve impairment of learning and memory in mice and/or rats. In this study, the effects of KT-95 were investigated in an acetic acid-induced writhing test and scopolamine-induced memory impairment test using spontaneous alternation performance in a Y-maze and a step-down type passive avoidance test. Male ddY mice were treated with KT-95 (0.24-2.35 micromol/kg, s.c.) 30 min before the behavioral test. In the writhing test, the antinociceptive effect of KT-95 (2.35 micromol/kg) was completely antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but not by naloxone (3.05 micromol/kg, s.c.). KT-95 significantly improved the impairment of spontaneous alternation induced by scopolamine (1.65 micromol/kg, s.c.). The ameliorating effect of KT-95 was not antagonized by nor-BNI, but was almost completely antagonized by a selective sigma-receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100, 2.6 micromol/kg, i.p.). KT-95 also significantly improved scopolamine-induced learning and memory impairment in the passive avoidance test, although the effect was partial. Administration of KT-95 itself induced impairment of learning and memory. KT-95-induced impairment was not antagonized by naloxone, naltrindole, nor-BNI or NE-100 indicating that this impairment was not because of opioid receptor stimulation. These results suggested that although the KT-95-induced antinociceptive effect was mediated by kappa-opioid receptors, the KT-95-induced improvement in scopolamine-induced impairment of memory was mediated mainly via sigma-receptors and partially by kappa-opioid receptors.

Animals↗

[Effect of a cyclic analog of enkephalin on learning and memory in the mouse].

In experiments on mice, the effect of cyclic analogue of enkephalin (CAE) on the processes of learning and memory was studied in control animals and in animals with changed functional state of monoaminergic brain systems. Administration of the peptide to intact animals significantly accelerated the acquisition of conditioned reflexes of two-way avoidance and did not significantly affect the retention of these reflexes and their subsequent reproduction. Retention and reproduction of conditioned reflexes elaborated in one combination, was disturbed. Administration of iprazid did not eliminate the "accelerating effect" of CAE on the formation of conditioned reflexes of the two-way avoidance but sharply disturbed their retention. In such conditions, the amnesing iprazid effect increased still more. Besides, under CAE effect, the activity of acetylcholinesterase in the motor and especially in the visual cortex of the mice increased. The obtained data testify to an important role of the monoaminergic and cholinergic brain mechanisms in realization of CAE effects on the processes of learning and memory.

Acetylcholinesterase↗

Decreased odor avoidance after electric shock in Drosophila mutants biases learning and memory tests.

The Drosophila mutants amnesiac, dunce (dnc), and rutabaga were isolated after associative conditioning tests, during which animals were trained to associate the presence of an odor with that of electric shocks (ES). In the absence of conditioning, the odor avoidance (OA) of these mutants was shown to be normal, indicating that their poor associative conditioning performance was attributable to specific learning or memory deficits. However, I show that the OA of the mutants is greatly decreased after their exposure to ES. This effect can last for hours. These results strongly suggest that part of the defect displayed by these mutants in associative conditioning tests does not correspond to a learning or memory deficit but might arise from abnormal sensitivity to stressful stimuli. I looked at the OA after ES of two previously characterized dnc mutants. Df(1)N79f specifically decreases Dnc expression in the mushroom bodies, leading to a normal level of learning but decreased memory. Df(1)N79f mutants displayed a normal OA after ES. Df(1)N64j15 affects the entire brain expression of Dnc, leading to decreased learning and memory. Df(1)N64j15 animals showed a strong decrease of their OA after ES. Thus, the lack of Dnc "general" expression is most likely responsible for the OA defect, which would be responsible for the apparent learning defect after conditioning. In contrast, the Dnc phosphodiesterase accumulated in the mushroom bodies would be involved specifically in memory formation.

Amnesia↗

Disturbance of learning and memory by the alkylation of muscarinic acetylcholine receptors by propylbenzilylcholine mustard.

The effects of blockade of muscarinic acetylcholine receptors (mAChR) in rat cerebral cortex on learning and memory were studied by the use of passive and active avoidance tests. Injection of propylbenzilylcholine mustard (PrBCM) into frontal, parietal and occipital cortex decreased mAChR dose dependently, as assessed by 3H-quinuclidinylbenzilate binding studies. Bilateral injection of PrBCM into frontal and/or parietal but not occipital cortex impaired passive avoidance learning. The results suggest that intact muscarinic neurotransmission is important for registration and recall, but not retention phases of the learning and memory process. Alkylation of mAChR by PrBCM also caused impairment in the performance of active avoidance task.

Alkylation↗

Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging.

Aging is a general process of functional decline which involves in particular a decline of cognitive abilities. However, the severity of this decline differs from one subject to another and inter-individual differences have been reported in humans and animals. These differences are of great interest especially as concerns investigation of the neurobiological factors involved in cognitive aging. Intensive pharmacological studies suggest that neurosteroids, which are steroids synthesized in the brain in an independent manner from peripheral steroid sources, could be involved in learning and memory processes. This review summarizes data in animals and humans in favor of a role of neurosteroids in cognitive aging. Studies in animals demonstrated that the neurosteroids pregnenolone (PREG) and dehydroepiandrosterone (DHEA), as sulfate derivatives (PREGS and DHEAS, respectively), display memory-enhancing properties in aged rodents. Moreover, it was recently shown that memory performance was correlated with PREGS levels in the hippocampus of 24-month-old rats. Human studies, however, have reported contradictory results. First, improvement of learning and memory dysfunction was found after DHEA administration to individuals with low DHEAS levels, but other studies failed to detect significant cognitive effects after DHEA administration. Second, cognitive dysfunctions have been associated with low DHEAS levels, high DHEAS levels, or high DHEA levels; while in other studies, no relationship was found. As future research perspectives, we propose the use of new methods of quantification of neurosteroids as a useful tool for understanding their respective role in improving learning and memory impairments associated with normal aging and/or with pathological aging, such as Alzheimer's disease.

Aging↗

Differential effects of anxiogenic central and peripheral benzodiazepine receptor ligands in tests of learning and memory.

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4'-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies.

Animals↗

Effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory and learning in immature rats.

Status epilepticus (SE) can be harmful to the developing brain. Our knowledge of the emotional and behavioral consequences of generalized SE in developing animals remains limited. Therefore, we investigated the short- and long-term effects of pentylenetetrazole (PTZ)-induced SE on emotional memory and learning and behavioral parameters in immature rats. SE was induced in 16- to 20-day-old rats (P16-P20) using intraperitoneal injections of PTZ (n=21); control rats received saline (n=10). All animals were tested using an elevated T-maze and open-field test 2, 14, 30, and 180 days after SE, to evaluate emotional memory and learning and behavior. Anxiety levels decreased 2 and 14 days after SE, and conditioned learning of PTZ-treated immature rats was better than that of the control rats. These results indicate that a decreased anxiety level facilitates conditioned learning. Behavioral changes are transient, and no emotional memory or learning deficits occur following PTZ-induced SE in immature rats.

Animals↗

[Effect of aluminum trichloride on dissociated Ca2+ in Hippocampus neuron cell as well as learning and memory].

OBJECTIVE: To investigate the effect of aluminum chloride on dissociated Ca(2+) in hippocampus neuron cells in mice and the relationship to the learning and memory. METHODS: Male ICR mice in the three intoxicated groups were administered with the double distilled water containing AlCl(3) (10, 50, 300 mg.kg(-1).d(-1)) while those in the control group were administered with the double distilled water for 100 days. The methods of behavior toxicology such as Morris swim maze were used for studying the effect of aluminum chloride on the changes of learning and memory in mice. With calcium sensitive fluorescence indicator Fura-2 as the fluorescent probe, the influence of the subchronic exposure to Al on the dissociated Ca(2+) in hippocampus neuron cells was observed. RESULTS: The dissociated Ca(2+) in hippocampus neuron cells in the middle dosage group and the high dosage group [(412.25 +/- 53.20), (467.37 +/- 32.85) times] was lower than those in the control group [(293.91 +/- 32.21) times] respectively (P < 0.01), and correlated positively with the dose and dissociated Ca(2+) (r = 0.861, P < 0.01). Compared with the control group, the latent period was lengthened (P < 0.05) in the middle dosage and the high dosage group. CONCLUSION: The subchronic exposure to AlCl(3) in mice affects the dissociated Ca(2+) in hippocampus neuron cells. The increase of dissociated Ca(2+) in hippocampus neuron cells may be correlated with the disfunction of cognition in the aluminium intoxicated mice.

Aluminum Chloride↗

Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release.

Pharmacological manipulation of N-methyl-D-aspartate (NMDA) receptors may be critical for the treatment of many neurological and psychiatric disorders. Metabotropic glutamate (mGlu5) receptors are abundant in corticolimbic circuitry, where they modulate NMDA receptor-mediated signal transduction. Therefore, pharmacological manipulation of mGlu5 receptor may provide a treatment strategy for cognitive disorders that are associated with NMDA receptor dysfunction. We sought to determine whether the recently described molecular and cellular interactions between NMDA and mGlu5 receptors coregulate higher order behaviors. We examined the interaction of the selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and the use-dependent NMDA antagonist MK-801, on locomotion, stereotypy, working memory, instrumental learning, and corticolimbic dopamine release. MPEP, at 10 mg/kg, but not 3 mg/kg, impaired working memory and instrumental learning, transiently increased dopamine release in prefrontal cortex and nucleus accumbens, and augmented the effect of MK-801 on cortical dopamine release, locomotion, and stereotypy. Pretreatment with 3 mg/kg of MPEP enhanced the detrimental effects of MK-801 on cognition. These results demonstrate that an mGlu5 receptor antagonist can potentiate the motoric, cognitive, and dopaminergic effects of an NMDA receptor antagonist. Thus, mGlu5 receptors appear to play a major role in regulating NMDA receptor-dependent cognitive functions such as learning and working memory. By extension, these results suggest that pharmacological potentiation of mGlu5 receptors may ameliorate the cognitive and other behavioral abnormalities associated with NMDA receptor deficiency.

Analysis of Variance↗

The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin-responsive adenylyl cyclase.

Four putative adenylyl cyclase genes from Drosophila melanogaster were identified by virtue of their extensive sequence homology with mammalian cyclases. One corresponds to the learning and memory gene rutabaga and is most similar to the mammalian brain Ca2+/calmodulin (CaM)-responsive cyclase. In a mammalian expression system, rutabaga cyclase activity was stimulated approximately 5-fold by the presence of Ca2+/CaM. A point mutation, identified at this locus in rut1 mutant flies, resulted in loss of detectable adenylyl cyclase activity. New P element insertion-induced rutabaga mutations mapped to within 200 nucleotides of the 5' end of the rutabaga cDNA. These data confirm the identity of the rutabaga locus as the structural gene for the Ca2+/CaM-responsive adenylyl cyclase and show that the inactivation of this cyclase leads to a learning and memory defect.

Adenylyl Cyclases↗

Behavioral consequences of intracerebral vasopressin and oxytocin: focus on learning and memory.

Since the pioneering work of David de Wied and his colleagues, the neuropeptides arginine vasopressin and oxytocin have been thought to play a pivotal role in behavioral regulation in general, and in learning and memory in particular. The present review focuses on the behavioral effects of intracerebral arginine vasopressin and oxytocin, with particular emphasis on the role of these neuropeptides as signals in interneuronal communication. We also discuss several methodological approaches that have been used to reveal the importance of these intracerebral neuropeptides as signals within signaling cascades. The literature suggests that arginine vasopressin improves, and oxytocin impairs, learning and memory. However, a critical analysis of the subject indicates the necessity for a revision of this generalized concept. We suggest that, depending on the behavioral test and the brain area under study, these endogenous neuropeptides are differentially involved in behavioral regulation; thus, generalizations derived from a single behavioral task should be avoided. In particular, recent studies on rodents indicate that socially relevant behaviors triggered by olfactory stimuli and paradigms in which the animals have to cope with an intense stressor (e.g., foot-shock motivated active or passive avoidance) are controlled by both arginine vasopressin and oxytocin released intracerebrally.

Animals↗

[Effects of hypoxia on AChE and NADPH-d levels in the marginal division and learning and memory functions of rats].

OBJECTIVE: To observe the pathological changes and changes in acetylcholinesterase (AChE) and reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) levels in the marginal division (MrD) following hypoxia, and explore the relation of hypoxia to damages of learning and memory functions. METHODS: Hypoxia models were established in 40 SD rats by treatment with the mixture of 8% oxygen and 92% nitrogen 5 times daily for 5 consecutive days, and the sham-hypoxia group was constituted by 10 rats receiving normal oxygen supply in the same manner as above. Another 10 untreated rats were used as normal control. The rats completing the hypoxia induction procedures were subjected to Y-maze test before their brain sections, along with those of the rats in the other 2 groups, were prepared for HE staining and immunohistochemical staining. RESULTS: AChE immunohistochemical results of the normal control group revealed numerous AChE-positive fibers and some positive cells in the striatum where the MrD was more lightly stained than the other regions. In the rats with hypoxia, however, the MrD was more intensely stained in comparison with the control, but the stain in other regions of the striatum did not manifest any significant differences between the groups. The MrD of normal rats possessed more NADPH-d-positive cells, all spindle-shaped, than the other regions of the striatum, and hypoxia did not result in morphological changes of the cells but significant reduction of their quantity occurred. CONCLUSION: Hypoxia may cause reduction of the learning and memory functions of rats and gives rise to alterations of AChE and NADPH-d staining patterns in the MrD. The MrD is more vulnerable to hypoxia as evidenced by more obvious changes in AChE and NADPH-d staining in the MrD than in the other regions of the striatum, which may be associated with the impairment of the learning and memory functions by hypoxia.

Acetylcholinesterase↗

The relationship between executive functioning and verbal and visual learning and memory.

Executive functions, which include an individual's ability to develop a response set, inhibit behaviors, plan, and reason, likely impact other areas of cognitive functioning, such as learning and memory. The present study examined the relationship between executive functioning and a wide array of standardized, clinical verbal and visual learning and memory measures in 212 patients referred for a neuropsychological evaluation. IQ was also included in the analyses. Results of the canonical correlation analyses indicated that the two cognitive domains shared 55-60% of variance, and two canonical variates were present. Although causality cannot be inferred, a clear and robust relationship between executive functioning and memory is evident, and clinicians should consider this overlap when interpreting poor performance among these two domains.

Adolescent↗

Spatial learning and memory in birds.

Behavioral ecologists, well versed in addressing functional aspects of behavior, are acknowledging more and more the attention they need also to pay to mechanistic processes. One of these is the role of cognition. Song learning and imprinting are familiar examples of behaviors for which cognition plays an important role, but attention is now turning to other behaviors and a wider diversity of species. We focus here on work that investigates the nature of spatial learning and memory in the context of behaviors such as foraging and food storing. We also briefly explore the difficulties of studying cognition in the field. The common thread to all of this work is the value of using psychological techniques as tools for assessing learning and memory abilities in order to address questions of interest to behavioral ecologists.

Animals↗