Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Investigação da relação entre conteúdo onírico e aprendizado de uma tarefa cognitiva complexa

Several lines of evidence indicate that sleep is beneficial for learning, but there is no experimental evidence yet that the content of dreams is adaptive, i.e., that dreams help the dreamer to cope with challenges of the following day. Our aim here is to investigate the role of dreams in the acquisition of a complex cognitive task. We investigated electroencephalographic recordings and dream reports of adult subjects exposed to a computer game comprising perceptual, motor, spatial, emotional and higher-level cognitive aspects (Doom). Subjects slept two nights in the sleep laboratory, a completely dark room with a comfortable bed and controlled temperature. Electroencephalographic recordings with 28 channels were continuously performed throughout the experiment to identify episodes of rapid-eye-movement (REM) sleep. Behaviors were continuously recorded in audio and video with an infrared camera. Dream reports were collected upon forced awakening from late REM sleep, and again in the morning after spontaneous awakening. On day 1, subjects were habituated to the sleep laboratory, no computer game was played, and negative controls for gamerelated dream reports were collected. On day 2, subjects played the computer game before and after sleep. Each game session lasted for an hour, and sleep for 7-9 hours. 9 different measures of performance indicated significant improve overnight. 81% of the subjects experienced intrusion of elements of the game into their dreams, including potentially adaptative strategies (insights). There was a linear correlation between performance and dream intrusion as well as for game improval and quantity of reported dreaming. In the electrophysiological analysis we mapped the subjects brain activities in different stages (SWS 1, REM 1, SWS 2, REM 2, Game 1 and Game 2), and found a modest reverberation in motor areas related to the joystick control during the sleep. When separated by gender, we found a significant difference on female subjects in the channels that indicate motor learning. Analysis of dream reports showed that the amount of gamerelated elements in dreams correlated with performance gains according to an inverted-U function analogous to the Yerkes-Dodson law that governs the relationship between arousal and learning. The results indicate that dreaming is an adaptive behavior

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

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

Identificação dos princípios ativos presentes no extrato etanólico de cereus jamacaru e avaliação em ratos dos possíveis efeitos tóxicos e/ou comportamentais da exposição prolongada

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Influência da idade, do sexo e da hora do dia no desempenho em teste de labirinto

The increase of elderly population in the world and in Brazil has indicated the necessity of health systems capable to evaluate, to diagnose and to intervene in the conditions of health and disease of that segment. During that stage of human development, physical and cognitive changes happen and they are capable to influence the functional acting. It s important to distinguish the limit between the normal and the pathological. Besides the common changes during the aging, biological rhithmicity changes happen, as alterations in the cycle vigil-sleep that can influence in certain tasks performance. This study aimed to verify the influence of the age, of the sex and of the hour in a maze test performance. Eighty individuals were evaluated, 40 youths (20 men and 20 women) and 40 senior (20 men and 20 women). They were separated in 2 different groups that were tested at 9:00 o clock and at 15:00 o clock. Initially they were submitted to health evaluation, cognitive evaluation and of sleep quality and chronotype. They were instructed to accomplish the maze test whose time of execution was timed and registered. Significant differences were observed according to age for the masculine group between elderly in the morning and in the afternoon and in the feminine group between youth and elderly in the test accomplished in the morning and in the afternoon. Significant differences were not observed according to sex and hour of the day and also between attempts. In compare between the 30th and the31st, accomplished in a 15minutes of interval, significant difference was observed just for the elderly group in the morning and in the afternoon. We observed significant correlations in the maze test performance with the cronotype, with the age, with the education and with the cognitive acting. The maze test was capable to detect differences between age in the acting profile and in the evaluation of the information maintenance after 15 minutes, however it was not possible to verify difference between sex and hour of the day. Finally the correlations of the maze test with another varied may indicate your importance as coadjutant instrument in those functions evaluation

Aprendizado espacial-temporal em um ambiente complexo sem restrição alimentar em ratos

Timeplace learning is the capacity of organisms to associate both space and time with a biological relevant stimulus such as food. Experiments are usually done with food restricted animals due to the belief that food system activation is necessary for timeplace learning. Another line of thought suggest that, in addition to food system activation, response cost should be increased to effectively allow timeplace discrimination. The purpose of this experiment was to test whether a complex environment, which presumably implied in a heightened response cost, would facilitate timeplace association in satiated rats using a highly palatable food as reward. Nine rats were trained in a timeplace task for 30 nonconsecutive days. A large experimental box (1x1m) divided in four compartments was used. To access each compartment the animal had to overcome a series of obstacles such as ramps, staircases and mazes. Two feeders localized in opposite compartments were rewarded with sunflower seeds in two daily sessions. One feeder offered the reward during the morning sessions while the second feeder in afternoon sessions. After the 15th day of training, the animals began to show a preference for the correct feeder during the correct time of day expressed by increased frequency of visits as well as lower latency to access the feeders. These results suggest that satiated animals are also capable of learning a timespace task as far as the experimental context is complex enough to result in a higher response cost

A cafeína exerce efeitos positivos sobre a memória tipo episódica em ratos adultos sem influenciar a sobrevivência neural no giro dentado

The caffeine is a mild psychostimulant that has positive cognitive effects at low doses, while promotes detrimental effects on these processes at higher doses. The episodic-like memory can be evaluated in rodents through hippocampus-dependent tasks. The dentate gyrus is a hippocampal subregion in which neurogenesis occurs in adults, and it is believed that this process is related to the function of patterns separation, such as the identification of spatial and temporal patterns when discriminating events. Furthermore, neurogenesis is influenced spatial and contextual learning tasks. Our goal was to evaluate the performance of male Wistar rats in episodic-like tasks after acute or chronic caffeine treatment (15mg/kg or 30mg/kg). Moreover, we assessed the chronic effect of the caffeine treatment, as well as the influence of the hippocampus-dependent learning tasks, on the survival of new-born neurons at the beginning of treatment. For this purpose, we used BrdU to label the new cells generated in the dentate gyrus. Regarding the acute treatment, we found that the saline group presented a tendency to have better spatial and temporal discrimination than caffeine groups. The chronic caffeine group 15 mg/kg (low dose) showed the best discrimination of the temporal aspect of episodic-like memory, whereas the chronic caffeine group 30mg/kg (high dose) was able to discriminate temporal order, only in a condition of greater difficulty. Assessment of neurogenesis using immunohistochemistry for evaluating survival of new-born neurons generated in the dentate gyrus revealed no difference among groups of chronic treatment. Thus, the positive mnemonic effects of the chronic caffeine treatment were not related to neuronal survival. However, another plastic mechanism could explain the positive mnemonic effect, given that there was no improvement in the acute caffeine groups

Neurofisiologia hipocampal durante sessões de sono intercaladas por exploração espacial: Reverberação do passado ou predição do futuro?

The ability to predict future rewards or threats is crucial for survival. Recent studies have addressed future event prediction by the hippocampus. Hippocampal neurons exhibit robust selectivity for spatial location. Thus, the activity of hippocampal neurons represents a cognitive map of space during navigation as well as during planning and recall. Spatial selectivity allows the hippocampus to be involved in the formation of spatial and episodic memories, including the sequential ordering of events. On the other hand, the discovery of reverberatory activity in multiple forebrain areas during slow wave and REM sleep underscored the role of sleep on the consolidation of recently acquired memory traces. To this date, there are no studies addressing whether neuronal activity in the hippocampus during sleep can predict regular environmental shifts. The aim of the present study was to investigate the activity of neuronal populations in the hippocampus during sleep sessions intercalated by spatial exploration periods, in which the location of reward changed in a predictable way. To this end, we performed the chronic implantation of 32-channel multielectrode arrays in the CA1 regions of the hippocampus in three male rats of the Wistar strain. In order to activate different neuronal subgroups at each cycle of the task, we exposed the animals to four spatial exploration sessions in a 4-arm elevated maze in which reward was delivered in a single arm per session. Reward location changed regularly at every session in a clockwise manner, traversing all the arms at the end of the daily recordings. Animals were recorded from 2-12 consecutive days. During spatial exploration of the 4-arm elevated maze, 67,5% of the recorded neurons showed firing rate differences across the maze arms. Furthermore, an average of 42% of the neurons showed increased correlation (R>0.3) between neuronal pairs in each arm. This allowed us to sort representative neuronal subgroups for each maze arm, and to analyze the activity of these subgroups across sleep sessions. We found that neuronal subgroups sorted by firing rate differences during spatial exploration sustained these differences across sleep sessions. This was not the case with neuronal subgroups sorted according to synchrony (correlation). In addition, the correlation levels between sleep sessions and waking patterns sampled in each arm were larger for the entire population of neurons than for the rate or synchrony subgroups. Neuronal activity during sleep of the entire neuronal population or subgroups did not show different correlations among the four arm mazes. On the other hand, we verified that neuronal activity during pre-exploration sleep sessions was significantly more similar to the activity patterns of the target arm than neuronal activity during pre-exploration sleep sessions. In other words, neuronal activity during sleep that precedes the task reflects more strongly the location of reward than neuronal activity during sleep that follows the task. Our results suggest that neuronal activity during sleep can predict regular environmental changes

Identidade, memória e narrativas na dança de São Gonçalo do povoado Mussuca (SE)

This study deals with the participation of the dance of São Gonçalo of the Mussuca town/SE, in the process of construction of the ethnic identity among this social group. The Mussuca is a grouping recognized as afro-descendents, linked with black enslaved people in the valley of the Cotinguiba region. The collective memory functions as a drive of this linking with the past and if it makes to elaborate narratives on this descent. The objective of this study was to investigate the ways the rite went through to constitute itself as an element of ethnic representation. Internal and external agents had been identified who had participated in different contexts. By means of an ethnographic work we ve reached some aspects of the local structure social which demonstrated the contradictions through the social relations of the group. This process of ethnic autorecognition presents the kinship and the space question as definers of the social arrangements which establish its ethnic boundaries

Vivendo do mar: tradição, memória e mudança na vida pesqueira de Pitangui-RN

This research focuses on the fishery activity, aligned to knowledge of past generations, and the transformation to those who depend on this activity for their livelihood, at the seashore community of Pitangui in Extremoz municipality, which lies 40 km away from Natal, seat of the state of Rio Grande do Norte. The intense modernization which has taking place during the last few years may be considered the result of a number of economic, social and cultural factors, as the introduction of new fishery technology. On the other hand, the present study seeks to show how this changing process happened, and to what extent those affected understand and evaluate this transformation. The methodology to carry out the ethnographic work was mainly adopted by qualitative methods and techniques - by participant observation, oral history, photography and the audiovisual records besides reference to data extracted under quantitative methods, as an important instrument of analyses. This induces a conclusion that the transformation of the community is a consequence of the globalized market, though still tied up to specific local relations. The emerging results are: the use of new fishery technology, and new ways of orientation and navigation; the opening to new jobs and occupational activity, the re-order of space s appropriation; changing sociability, larger access to consumer goods, besides bringing on some new conflicts land appropriation and the fishery and the protection of the environment. All this comprehended as a result of the movement of the local relations participating in the global spaces

Patrimônio, Memória e Espaço: a construção da paisagem açucareira do Vale do Ceará-Mirim

This work aims to understand how the installation of sugar culture along the river Ceará-Mirim defined the spatial organization of the Valley, and thus setting the landscape. This space has begun to be defined only in the second half of the nineteenth century, when the sugarcane growth had atarted on land located on the banks of the river Ceará-Mirim. The passage of this period of great prosperity can be seen through the heritage material which is still presented in the region. Walking through the Valley, we found a considerable number of architectural buildings, many in ruins, linked to this historical moment. This perception, caused by these buildings, will take us on a trip to the past, back to a time characterized by great-houses, mills, sugarcane plantations, planters, slaves, etc. The references that lead us to consider the sugar mills located along the valley of Ceará Mirim as a patrimony, which carry an entire historical baggage, guide us to the first half of the twentieth century. During this period, the role of intellectuals from the Rio - Sao Paulo through the modernist movement will be decisive in the formation of a national identity. The heritage material identified along the valley of Ceará Mirim defined its current spatial organization, setting the landscape. But we must conceive this landscape into two ways: first, as a material representation of social practices carried out in this space, where social, cultural, economic and environmental aspects have interacted to their training; as well as a landscape that carries a whole historical baggage which was built throughout the twentieth century

Diferenças funcionais das regiões hipocampais na formação da memória do tipo o quê", "quando" e "onde" em ratos

Episodic memory refers to the recollection of what, where and when a specific event occurred. Hippocampus is a key structure in this type of memory. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodic memories, while CA1 is involved in memory consolidation. However there are few studies with animal models that access simultaneously the aspects ‗what-where-when . Recently, an object recognition episodic-like memory task in rodents was proposed. This task consists of two sample trials and a test phase. In sample trial one, the rat is exposed to four copies of an object. In sample trial two, one hour later, the rat is exposed to four copies of a different object. In the test phase, 1 h later, two copies of each of the objects previously used are presented. One copy of the object used in sample trial one is located in a different place, and therefore it is expected to be the most explored object.However, the short retention delay of the task narrows its applications. This study verifies if this task can be evoked after 24h and whether the pharmacological inactivation of the DG/CA3 and CA1 subregions could differentially impair the acquisition of the task described. Validation of the task with a longer interval (24h) was accomplished (animals showed spatiotemporal object discrimination and scopolamine (1 mg/kg, ip) injected pos-training impaired performance). Afterwards, the GABA agonist muscimol, (0,250 μg/μl; volume = 0,5 μl) or saline were injected in the hippocampal subregions fifteen minutes before training. Pre-training inactivation of the DG/CA3 subregions impaired the spatial discrimination of the objects (‗where ), while the temporal discrimination (‗when ) was preserved. Rats treated with muscimol in the CA1 subregion explored all the objects equally well, irrespective of place or presentation time. Our results corroborate the computational models that postulate a role for DG/CA3 in spatial pattern separation, and a role for CA1 in the consolidation process of different mnemonic episodes

Oscilações Teta no hipocampo do rato durante tarefa de tomada de decisão espacial

The processing of spatial and episodic information during memory tasks depends on hippocampal theta oscillations. In the present study, I investigated the relationship between theta power and choice selection during spatial decision-making. I recorded local field potentials from the CA1 region of rats retrieving reward locations in a 4-arm maze. In trained but not in naïve animals, I observed a significant increase in theta power during decision-making, which could not be explained by changes in locomotion speed. Furthermore, a Bayesian decoder based on theta power predicted choice outcomes in speed-matched trials. The decoding time course revealed that performance increased above chance before the decision moment exclusively for theta power, remaining flat for other frequency bands. These results occurred for trained animals, but no significant prediction could be made for naïve animals. Altogether, the data support a mnemonic function of theta rhythm during spatial decision-making, indicating that these oscillations correlate with the retrieval of memories required for successful decisions

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed