Avaliação dos efeitos do biperideno, diazepam e neuropeptídeos S sobre a memória e a ansiedade na tarefa do labirinto em T elevado em camundongos

Anxiety is an emotional phenomenon, and normally it is interpreted as an adaptative behavior front to adversities. In its pathological form, anxiety can severely affect aspects related to the personal and professional life. Studies have shown a close relationship between anxiety disorders and aversive memory processing. Considering that the pharmacotherapy of anxiety disorders is still limited, innovative anxiolytic agents are needed. In this regard, neuropeptides systems are interesting therapeutic targets to the treatment of psychopathologies. Neuropeptide S (NPS), a 20-aminoacid peptide, is the endogenous ligand of a G-protein coupled receptor (NPSR), which has been reported to evoke hyperlocomotion, awakefull states, besides anxiolysis and memory improvements in rodents. This study aimed to investigate the effects of biperiden (BPR; an amnesic drug), diazepam (DZP; an anxiolytic drug) and NPS at three distinct times: pre-training, post-training, and pre-test, in order to assess anxiety and memory process in the same animal model. The elevated Tmaze (ETM) is an apparatus derived from the elevated plus-maze test, which consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300 s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. When injected pre-training, BPR (1 mg/kg) impaired learning and memory processing; DZP (1 and 2 mg/kg) evoked anxiolysis, but only at the dose of 2 mg/kg impaired memory; and NPS 0.1 nmol induced anxiolysis without affecting memory. Post-training injection of DZP (2 mg/kg) or BPR (1 and 3 mg/kg) did not affect memory consolidation, while the post-trainning administration of NPS 1 nmol, but not 0.1 nmol, improved memory in mice. Indeed, pre-trainning administration of NPS 1 nmol did not prevent memory impairment elicited by BPR (2 mg/kg, injected before training). In the open field test, BPR 1 mg/kg and NPS 1 nmol induced hyperlocomotion in mice. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs. The anxiolytic and memory enhancement effects of NPS were detected in the ETM task, and reinforce the role of NPS system as an interesting therapeutic target to the treatment of anxiety disorders

Alterações na evocação de uma memória aversiva ao liongo do ciclo estral de ratas: influências da transmissão gabaérgica na amígdala

GABAergic neurotransmission has been implicated in many aspects of learning and memory, as well as mood and anxiety disorders. The amygdala has been one of the major focuses in this area, given its essential role in modulating emotionally relevant memories. However, studies with male subjects are still predominant in the field. Here we investigated the consequences for an aversive memory of enhancing or decreasing GABAergic transmission in the basolateral nucleus of the amygdala (BLA). Wistar female rats were trained in the plus-maze discriminative avoidance task, in which they had to learn to avoid one of the enclosed arms where an aversive stimulus consisting of a bright light and a loud noise was given (day 1). Fifteen minutes before the test session (day 2) animals received 0,2 μL infusions of either saline solution, the GABAergic agonist muscimol (0,05 mg/ml), or the GABAergic antagonist bicuculine (0,025 mg/ml) bilaterally intra-BLA. On the test day, females in proestrous or estrous presented adequate retrieval and did not extinguish the task, while females in metestrous or diestrous presented impaired retrieval. In the first group, muscimol infusion impaired retrieval and bicuculline had no effect, suggesting naturally low levels of GABAergic transmission in the BLA of proestrous and estrous females. In the second group, muscimol infusion had no effect and bicuculline reversed retrieval impairment, suggesting naturally high levels of GABAergic transmission in the BLA of metestrous and diestous females. Additionally, proestrous and estrous females presented higher anxiety levels compared to metestrous and diestrous females, which could explain better performance of this group. On the other hand, BLA GABAergic system did not interfere with the innate fear response because drug infusions had no effect in anxiety. Thus, retrieval alterations caused by the GABAergic drugs were probably related specifically to memory processes

Álcool e comportamento: efeitos na aprendizagem e memória

Excessive alcohol consumption is responsible for many harmful effects on individuals and society. Despite years of research, the mechanisms by which alcohol affects neurological functions and the exact causes of cognitive impairment related to long-term use are unknown. In this sense, this master study proposed to observe how different doses of alcohol affect the addiction response and the learning ability of two fish species: Betta splendens and Danio rerio, the latter a commonly model due to organizational and functional characteristics shared with mammals. For this, different concentrations of ethanol (0%, 0.1%, 0.25%, 1% and 1.5%) were used in acute, chronic and withdrawal treatments. We tested the fish in three experimental protocols: 1) alcohol addiction potential using conditioned place preference, 2) associative conditioning using light as unconditioned stimulus and food as conditioned stimulus and 3) spatial learning using a maze without cues. For the alcohol addiction potential, preference between two different places in a shuttle box was tested before and after alcohol exposure (chronic and acute). In this test, the animals intoxicated by 0.1% did not change behavior, while animals receiving 1% and 1.5% alcohol changed the initial preference to the side where they received alcohol For the associative conditioning, the results show that the groups undergoing low dose (0.1%), both in chronic and withdrawal treatment, learned the task faster than control; groups under 0.25 and 1% alcohol withdrawal learned the task after control; groups chronically intoxicated with these doses did not learn the task. For the spatial learning test, fish submitted to acute and chronic treatments decreased the time to exit the maze; there were significant differences in the animal s performance in a dose-dependent pattern. This difference was not observed for the withdrawal treatment. Given these results, we conclude that the effects of alcohol on learning are dependent on the dosage. Furthermore, low doses of alcohol seem to maximize animal performance on learning tasks and do not alter their seeking behavior, while higher doses induced addition and hinder learning

Efeitos de diferentes tipos estressores sobre a memória e aprendizagem de ratas

The exposure to stressors produces physiological changes of the organism in order to adapt the individual to the environment. Depending on the type, intensity and duration, stress can affect some cognitive functions, particularly processes of learning and memory. Several studies have also proposed that some level of anxiety would be necessary for memory formation. In this context, memories of previously aversive experiences may determine the manner and intensity with which are expressed fear responses, which explains the great interest in analyzing both anxiety and memory in animals. In addition, males and females demonstrate different reactions in relation to stressful stimuli, showing different levels of anxiety and differences in processing of the acquisition, retention and recall of information. Based on this information, the present study aimed to verify the effect of stress on learning, memory and anxiety behavioral parameters in rats exposed at different types of stressors of long duration (seven consecutive days): restraint (4h/day), overcrowding (18h/day) and social isolation (18h/day) in the different phases of the estrous cycle. Our results showed that the stress induced by restraint and social isolation did not cause changes in the acquisition process, but impaired the recall of memory in rats. Furthermore, it is suggested a protective effect of sex hormones on retrieval of aversive memory, since female rats in proestrus or estrus phase, characterized by high estrogen concentrations, showed no aversive memory deficits. Furthermore, despite the increased plasma levels of corticosterone observed in female rats subjected to restraint stress and social isolation, anxiety levels were unaltered, compared to those various stress conditions. Animal models based on psychological and social stress have been extensively discussed in the literature. Correlate behavioral responses, physiological and psychological have contributed in increasing the understanding of stress-induced psychophysiological disorders

Memória de reconhecimento em indivíduos adultos com mais de 45 anos

As we grow old, there are many cognitive processes which decline in the human brain. One of them is the memory, a function that allows retention and posterior use of knowledge learned during the life, understood as a result of multiple systems highly organized and spread in several neural regions. This work aimed to evaluate the recognition memory in adults over 45 years old through words and pictures recognition tasks and the use of two codification or learning conditions (same distracters and different distracters). Twelve individuals were studied (6 men and 6 women) aged between 45 and 88 years old and with similar demographic characteristics. They presented better performance on picture tasks rather than word tasks. Better results were also verified when the codification context had different distracters, which significantly reflected in a long term principally in elderly individuals. The results reached suggest that the codification context influenced the lists of pictures and words learning, mainly for the elderly ones, when compared to adults, and that these results can be related to the phenomena involved with the recognition memory, the recollection and familiarity

O Tratamento com a fluoxetina (mas não com outros farmacos antidepressivo e ansioíiticos) reverte o déficit de memória aversiva causado por estresse agudo de contenção em camundongos

The physiologist H. Selye defined stress as the nonspecific response of the body to any factors that endanger homeostasis (balance of internal environment) of the individual. These factors, agents stressors, are able to activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, thus resulting in the physiological responses to stress by the release of glucocorticoids that leads to psychophysiological changes, including effects on cognitive functions such as learning and memory. When this axis is acutely stimulated occurs a repertoire of behavioral and physiological changes can be adaptive to the individual. Notwithstanding, when the HPA axis is chronically stimulated, changes may favor the development of, such as anxiety disorders. Some drugs used in the clinic for the treatment of anxiety disorders these can exert effects on cognitive function, on the HPA axis and on the anxiety. In this context, the aim of our study was to investigate the effects of administration i.p. acute of diazepam (DZP, 2 mg/kg), buspirone (BUS, 3 mg/kg), mirtazapine (MIR, 10 mg/kg) and fluoxetine (FLU, 10 mg/kg) in male mice submitted to acute restraint stress, and evaluated using plus-maze discriminative avoidance task (PMDAT), which simultaneously evaluates parameters such as learning, memory and anxiety. Our results demonstrated that (1) the administration of DZP and BUS, but not FLU, promoted anxiolytic effects in animals; (2) administration mirtazapine caused sedative effect to animals; (3) in the training session, the animals treated with BUS, MIR and FLU learned the task, on the other hand DZP group showed impairment in learning; (4) in the test session, animals treated with DZP, BUS, and MIR showed deficits in relation to discrimination between the enclosed arms, aversive versus non-aversive arm, demonstrating an impairment in memory, however, animals treated with FLU showed no interference in the retrieval of this memory; (5) acute stress did not interfere in locomotor activity, anxiety, or learning on the learning task, but induced impairment in retrieval memory, and the group treated with FLU did not demonstrated this deficit of memory . These results suggest that acute administration of drugs with anxiolytic and antidepressant activity does not interfere with the learning process this aversive task, but impair its retrieval, as well as the acute restraint stress. However, the antidepressant fluoxetine was able to reverse memory deficits promoted by acute stress, which may suggest that modulation, even acutely serotonergic neurotransmission, by selectively inhibiting the reuptake of this neurotransmitter, interferes on the process of retrieval of an aversive memory

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

Efeito do alerta e valência emocional nos componentes de lembrança e familiaridade da memória episódica

The episodic memory system allows us to retrieve information about events, including its contextual aspects. It has been suggested that episodic memory is composed by two independent components: recollection and familiarity. Recollection is related to the vivid e detailed retrieval of item and contextual information, while familiarity is the capability to recognize items previously seen as familiars. Despite the fact that emotion is one of the most influent process on memory, only a few studies have investigated its effect on recollection and familiarity. Another limitation of studies about the effect of emotion on memory is that the majority of them have not adequately considered the differential effects of arousal and positive/negative valence. The main purpose of the current work is to investigate the independent effect of emotional valence and arousal on recollection and familiarity, as well as to test some hypothesis that have been suggested about the effect of emotion on episodic memory. The participants of the research performed a recognition task for three lists of emotional pictures: high arousal negative, high arousal positive and low arousal positive. At the test session, participants also rated the confidence level of their responses. The confidence ratings were used to plot ROC curves and estimate the contributions of recollection and familiarity of recognition performance. As the main results, we found that negative valence enhanced the component of recollection without any effect on familiarity or recognition accuracy. Arousal did not affect recognition performance or their components, but high arousal was associated with a higher proportion of false memories. This work highlight the importance of to consider both the emotional dimensions and episodic memory components in the study of emotion effect on episodic memory, since they interact in complex and independent way

Estampa temporal na memória de reconhecimento em estudantes universitários

Several studies have shown that there is a circadian modulation of explicit memory. This modulation can occur independently in each one of the mnemonic processes. The aim of this study was to evaluate the influence of time of training on short-term memory (STM) and long-term memory (LTM), using a recognition task. Moreover, a possible circadian modulation in retrieving was investigated when this process matched the acquisition hour (time stamp). The chronotype variable was also considered. Fifty-seven undergraduate students aging between 18 and 25 years (21,72 ± 2,14; 28 ♂) participated in this study. In the training phase (acquisition) the subjects heard a ten word list. Following this, they answered a recognition test to evaluate STM and one week later they answered a recognition test to evaluate LTM. In each chronotype, the subjects were divided in groups according to the training hour, part of them in the morning and the other in the afternoon. One week later some of the subjects in each group underwent LTM testing in the morning and others in the afternoon. When the subjects performances were analyzed together, independently of the chronotypes, a training hour effect was found in the LTM. The subjects trained in the afternoon had better performance. No time of day effect was found in the STM and in retrieving from the LTM. However, the morning types who were trained and tested in the same hour had a better performance in the LTM when compared to morning types trained and tested in different hours. This effect did not occur when the other chronotypes were analyzed. The circadian modulation seems to occur at least in two different ways. First, there is a circadian modulation in the acquisition/consolidation processes, with a better performance occuring in the afternoon. Secondly, there is a modulation in the retrieval mnemonic process, called time stamp phenomenon. This phenomenon, that occurred in the morning types, is showed for the first time in humans

Investigação da memória autobiográfica em idosos com demência de Alzheimer nas fases leve e moderada

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fenótipo neuropsicológico de adolescentes com síndrome de Down

This research aimed to contribute to the characterization of a neuropsychological phenotype of adolescents with Down Syndrome (DS). A multicases study of six adolescents (three males and three females, aged 13 to 14 years) diagnosed with DS and treated at two institutions in the city of Natal (Brazil), was conducted. Participants were assessed using the methodological approach developed by Luria, which is composed by four complementary stages. The first one aimed to investigate the qualitative impact of DS in school life and social development of the adolescents; dimensions of behavior and social-affective aspects of the members of the study were investigated. In the second stage participants performed a battery of neuropsychological tests in order to identify strengths and weaknesses in their cognitive functioning. The third stage was incorporated into the second in order to analyze the quality of the activity of the participants along the quantitative evaluation, highlighting strategies used, errors produced among other indicators. Lastly, the fourth stage refers to the intervention with the participants. Although this is not a specific objective of the study, it is argued that the outcome of this research will subsidize the practice of different professionals working with this clinical group. The results of the first stage emphasized the presence of difficulties in social relationships and in school life of observed adolescents. In turn, the second and third stages pointed out to the presence of difficulties in tasks involving logical and abstract thinking, as well as difficulties in expressive language. In relation to visual memory, we observed a better performance in activities of lower complexity, ie, with less interference of executive functioning, particularly in terms of the functions of planning and initiative. Finally, it was found motor and mental retardation, affecting significantly the performance related to different cognitive areas. The results highlighted here can be considered as subsidies for future interventions, suggesting the need for developping projects that take into account different aspects constituents of the human subject, involving not only the individual with developmental changes, as well as their families, teachers, schools and society in general

Uma estratégia dirigida a modelos e baseada em linguagem de descrição arquitetural para linhas de produtos de software

Model-oriented strategies have been used to facilitate products customization in the software products lines (SPL) context and to generate the source code of these derived products through variability management. Most of these strategies use an UML (Unified Modeling Language)-based model specification. Despite its wide application, the UML-based model specification has some limitations such as the fact that it is essentially graphic, presents deficiencies regarding the precise description of the system architecture semantic representation, and generates a large model, thus hampering the visualization and comprehension of the system elements. In contrast, architecture description languages (ADLs) provide graphic and textual support for the structural representation of architectural elements, their constraints and interactions. This thesis introduces ArchSPL-MDD, a model-driven strategy in which models are specified and configured by using the LightPL-ACME ADL. Such strategy is associated to a generic process with systematic activities that enable to automatically generate customized source code from the product model. ArchSPLMDD strategy integrates aspect-oriented software development (AOSD), modeldriven development (MDD) and SPL, thus enabling the explicit modeling as well as the modularization of variabilities and crosscutting concerns. The process is instantiated by the ArchSPL-MDD tool, which supports the specification of domain models (the focus of the development) in LightPL-ACME. The ArchSPL-MDD uses the Ginga Digital TV middleware as case study. In order to evaluate the efficiency, applicability, expressiveness, and complexity of the ArchSPL-MDD strategy, a controlled experiment was carried out in order to evaluate and compare the ArchSPL-MDD tool with the GingaForAll tool, which instantiates the process that is part of the GingaForAll UML-based strategy. Both tools were used for configuring the products of Ginga SPL and generating the product source code

Uma linguagem de modelagem da interação para auxiliar a comunicação designer-usuário

The development of interactive systems involves several professionals and the integration between them normally uses common artifacts, such as models, that drive the development process. In the model-driven development approach, the interaction model is an artifact that includes the most of the aspects related to what and how the user can do while he/she interacting with the system. Furthermore, the interactive model may be used to identify usability problems at design time. Therefore, the central problematic addressed by this thesis is twofold. In the first place, the interaction modeling, in a perspective that helps the designer to explicit to developer, who will implement the interface, the aspcts related to the interaction process. In the second place, the anticipated identification of usability problems, that aims to reduce the application final costs. To achieve these goals, this work presents (i) the ALaDIM language, that aims to help the designer on the conception, representation and validation of his interactive message models; (ii) the ALaDIM editor, which was built using the EMF (Eclipse Modeling Framework) and its standardized technologies by OMG (Object Management Group); and (iii) the ALaDIM inspection method, which allows the anticipated identification of usability problems using ALaDIM models. ALaDIM language and editor were respectively specified and implemented using the OMG standards and they can be used in MDA (Model Driven Architecture) activities. Beyond that, we evaluated both ALaDIM language and editor using a CDN (Cognitive Dimensions of Notations) analysis. Finally, this work reports an experiment that validated the ALaDIM inspection method

O uso de linguagem documentária em catálogos coletivos de bibliotecas universitárias: um estudo de avaliação sociocognitiva com protocolo verbal

Avaliou-se o uso de linguagem documentária alfabética de catálogos coletivos, na perspectiva das bibliotecas universitárias e no contexto sociocognitivo dos indexadores e dos usuários. Concluiu-se que o uso adequado de linguagens documentárias de áreas científicas especializadas faz-se por meio da avaliação quanto à atualização, especificidade e compatibilidade para atender às necessidades de indexação e recuperação da informação.

Produção de conhecimento sobre narrativas orais: contribuições para as investigações em linguagem infantil

Este estudo tem como objetivo indicar um panorama geral sobre a produção de conhecimento no que tange os padrões para o desenvolvimento da narrativa oral, nos últimos quatro anos por meio de uma revisão bibliográfica sistematizada, voltada para a temática de intervenção em linguagem infantil, com o uso de narrativas orais. A revisão foi realizada em uma única etapa, com critérios específicos, utilizando os seguintes descritores: narrativas, narrativa, narrativas de crianças, linguagem e desenvolvimento, linguagem oral, habilidades linguísticas, linguagem falada, linguagem infantil, narração/narração de histórias e linguagem. O período considerado foi de 2007 a 2011. Foram obtidos 900 registros, dentre os quais, nove (1%) atenderam aos critérios estabelecidos para análise. A maioria dos estudos relacionou-se com análises psicolinguísticas. Apenas um estudo utilizou método experimental. No período considerado foram produzidos poucos estudos abordando narrativas orais infantis; a sua grande maioria levou em consideração, fundamentalmente, aspectos cognitivos e linguísticos no processo de desenvolvimento da habilidade narrativa; a grande maioria das pesquisas foi realizada com crianças que possuem algum tipo de alteração em seu desenvolvimento linguístico. Considera-se que a produção de conhecimento, em relação ao desenvolvimento de narrativas orais infantis, exige, atualmente, um olhar voltado para as intervenções que utilizem metodologia experimental. Por fim, considera-se que é necessária uma atenção maior em relação ao desenvolvimento típico da habilidade narrativa.