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

Efeitos da alteração dos níveis de ansiedade no desempenho de ratos em uma tarefa de discriminação apetitiva

The plus-maze discriminative avoidance paradigm has been used to study the relationship between aversive memory and anxiety. The present study aims to verify if the elevated plus-maze can provide information about appetitive memory and anxiety, through a task motivated by food reward. Animals were allowed to explore an elevated plus-maze and received reinforcement in one of the enclosed arms. In a test session performed 24h later, in the absence of reward, rats showed preference for the previously rewarded enclosed arm over the neutral enclosed arm. The administration of diazepam and pentylenetetrazole before training induced, respectively, anxiolytic and anxiogenic effects (as evaluated by open-arm exploration). Both drugs induced amnestic effects, i.e., lack of preference for the rewarded arm in the test session. The results suggest that appetitive memory can be influenced by anxiety levels as well. The plus-maze appetitive discrimination task seems to be a useful model to investigate the relationship between memory and anxiety

Efeitos de vocalizações de co-específicos e do escuro sobre o ritmo circadiano da atividade motora em sagüis (Callithrix jacchus)

The principal zeitgeber for most of species is the light-dark photocycle (LD), though other environment factors as food availability, temperature and social cues may act. Daily adjustment of the circadian pacemaker may result from integration of environmental photic and non-photic cues with homeostatic cues. Characterization of non-photic effects on circadian timing system in diurnal mammals is scarce in relation to nocturnal, especially for ecologically significant cues. Thus, we analyzed the effect of conspecific vocalizations and darkness on circadian activity rhythm (CAR) in the diurnal primate Callithirx jacchus. With this objective 7 male adults were isolated in a room with controlled illumination, temperature (26,8 ± 0,2°C) and humidity (81,6 ± 3,6%), and partial acoustic isolation. Initially they were under LD 12:12 (~300:2 lux), and subsequently under constant illumination (~2 lux). Two pulses of conspecific vocalizations were applied in total darkness, separated by 22 days, at 7:30 h (external time) during 1 h. They induced phase delays at circadian times (CTs) 1 and 10 and predominantly phase advances at CTs 9 and 15. After that, two dark pulses were applied, separated by 14 days, during 1 h at 7:30 h (external time). These pulses induced phase delays at CTs 2, 3 and 18, predominantly phase advances at CTs 8, 10 and 19, and no change at CT 14. However, marmosets CAR showed oscillations in endogenous period and active phase duration influenced by vocalizations from animals outside the experimental room, which interfered on the phase responses to pulses. Furthermore, social masking and relative coordination with colony were observed. Therefore, phase responses obtained in this work cannot be attributed only to pulses. Afterwards, pulses of conspecific vocalizations were applied in total darkness at 19:00 h (external time), during 1 h for 5 consecutive days, and after 21 days, for 30 consecutive days, on attempt to synchronize the CAR. No animal was synchronized by these daily pulses, although oscillations in endogenous period were observed for all. This result may be due to habituation. Other possibility is the absence of social significance of the vocalizations for the animals due to random reproduction, since each vocalization has a function that could be lost by a mixture of sounds. In conclusion, conspecific vocalizations induce social masking and relative coordination in marmosets CAR, acting as weak zeitgeber

Efeitos da cafeína sobre a memória de saguis (Callithrix jacchus)

Caffeine is considered the most consumed psychostimulant in the world, presenting several central and peripheral effects. In the Central Nervous System the major effect occur by its antagonistic activity at the A1 and A2a subtypes of the adenosine receptors. These receptors are responsible for the slow-wave sleep induction, and their binding, caused by the consumption of foods and beverages that contain caffeine, cause behaviors like increase of alertness, mood and locomotion. The effects of caffeine on memory are still discussed because of the diversity of experimental protocols. Also, it does not have the same effects on all stages of the processing of memory - acquisition, consolidation and recall. Thus, using the marmoset (Callitrhix jacchus) as subject, we aim to evaluate the effects of caffeine on the memory of this primate through the conditioned place preference paradigm, where the animal selects a context by presence of food. This cognitive task consists of five phases. The first phase was two sessions of pre-exposure, in which they were evaluated for preference for any compartment of the apparatus. Then, we proceeded the training, conditioning the animals to the food-present context for 8 days. Then, there was administration of caffeine or placebo (10mg/kg) for 8 consecutive days, during the pre-sleep phase, where the 20 animals were distributed in two groups: placebo and repeated. The forth phase was one day of retraining, a re-exposure of the apparatus to the marmosets followed by the administration of caffeine (for the repeated group and a new group called abstinence) or placebo (for placebo and abstinence groups). Finally, was the test where we evaluated if the subjects learned where the food was present. Moreover, in this work we evaluate the existence of differences between females and males on the task, and the locomotor activity for the experimental groups. The results showed that in the pre-exposure phase the animals were habituated on the apparatus and did not present differences for any contexts. In training, they were able to learn the conditioning task, independent of gender. For the retraining, the two groups exhibited more interactions in rewarded context than that in non-rewarded context. Nevertheless, in the locomotor activity, the repeated group moved similarly in contact with the apparatus and outside of it. In the other hand, the animals of the placebo group moved more when in contact with the apparatus. In the test phase, the marmosets under influence of caffeine presented an increase in the locomotor activity when compared with the placebo group, corroborating works that show this increase in locomotion. In the learning evaluation, the continuous and abstinence groups had a bad performance in the task in relation to the placebo and acute groups. This suggests that the prolonged administration of caffeine disrupts the memories because it affected sleep, which is largely responsible offline processing of memories

Comportamento social de botos-cinza, sotalia guianensis, na praia de Pipa, RN, Brasil: dinâmica, sequência, sincronia e respostas ao turismo de observação

Social behavior of Guiana dolphins, Sotalia guianensis, at Pipa Beach, RN, Brazil: dynamics, sequence, breathing synchrony, and responses to dolphin watching. Social animals form groups that can range from temporary to permanent. Depending on the nature of the social relationships developed between individuals, groups present a particular social organization and the effect of these interactions shapes the activity patterns of these animals. This study investigates: (i) fission-fusion dynamics of Guiana dolphins, through the analysis of three dimensions of the social system (variation in spatial cohesion, variation in size and composition of groups), (ii) sequence, routine and behavioral stability, (iii) breathing intervals in synchronized groups and (iv) behavioral responses of the animals to dolphin watching. Systematic observations of Guiana dolphins were made from a platform located in cliffs about 25 m above sea level that surround Madeiro Bay, Pipa Beach. Sampling occurred from December 2007 to February 2009 between 0600 h and 1600 h, and the groups of Guiana dolphins were investigated according to their size (alone and group) and composition (adults, adults and juveniles, and adults and calves). According to the analysis of fission-fusion dynamics, Guiana dolphin groups frequently changed their composition, modifying their patterns of spatial grouping and cohesion every 20 minutes on average. More than 50% of the individuals maintained a distance of up to 2 m from other group members and new individuals were attracted to the group, especially during feeding, leaving it for foraging. Large groups were more unstable than small, while groups containing only adults were more stable than groups of adults and juveniles. According to the Z-score analysis to investigate the sequence and behavioral routine, lone individuals were more ! .7! ! involved in foraging and feeding, while resting was more common in groups. Foraging and feeding were more common in homogeneous groups (individuals of the same age class), while heterogeneous groups (different age classes) were often involved in socialization, displaying a broader behavioral repertoire. Foraging and resting behavior presented higher stability (continuous duration in minutes) than the other behaviors. The analysis of breathing intervals in synchronized groups showed significant differences depending on type of behavior, composition and area preference. During resting, breathing intervals were of longer duration, and groups with calves showed shorter breathing intervals than groups without calves. Lone individuals also preferred areas called corral , often used for the entrapment of fishes. The Markov chain analysis revealed behavioral changes in the presence of boats, according to the type of group composition. Groups composed of adults presented decreased resting and increased in traveling during the presence of boats. Groups of adults and juveniles showed a massive reduction of socialization, while the behavior transition probability traveling-traveling was higher in groups of adults and calves. In the presence of the boats, stability of resting was reduced by one third of its original duration and traveling more than doubled. The behavioral patterns analyzed are discussed in light of socio-ecological models concerning costs and benefits of proximity between individuals and behavioral optimization. Furthermore, significant changes in behavioral patterns indicate that Guiana dolphins, at Pipa Beach, have suffered the effects of tourism as a result of violation of rules of conduct established for the study area

Proposta de Intervenção para Auxiliar a Reabilitação Motora e Cognitiva de Pacientes com Acidente Vascular Cerebral

Stroke is the leading cause of combined motor and cognitive disability worldwide. The rehabilitation of stroke patients is mostly directed towards motor recovery through the training of the affected member under supervision of a Physical Therapist. In the present study we introduce a new approach for both cognitive and motor therapy, which relies on motor imagery of the upper limbs and working memory training. This therapy should be utilized as an adjuvant to physical therapy. Ten individuals (5 men and 5 women) were selected for the pilot study, all of them in the acute phase of the first ischemic stroke episode. The control group had 5 individuals who were submitted to physical therapy only, whilst the other 5 patients in the experimental group also performed the cognitive and motor training with a video game specially built for this study. Two patients left the experimental group before the end. Total training lasted for 9 weeks, 2 times a week, for half an hour. Patients reported they enjoyed playing the game, even though it required a lot of mental effort, according to them. Plus, they considered it had a beneficial influence in their activities of daily living. No side effects were reported. Preliminary results suggest there is a difference between groups in cognitive and upper limb motor evaluation following the intervention. It is important to notice that our conclusions are limited due the small sample number. Overall, this work is supported by other studies in literature focused in rehabilitation with motor imagery and working memory and indicate a continuity of the research, increasing total training hours

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

Estudo dos efeitos comportamentais do neuropeptídeos em camundongos submetidos a modelos animais de Parkinson

Neuropeptide S (NPS) is the endogenous ligand of a G-protein coupled receptor. Preclinical studies have shown that NPSR receptor activation can promote arousal, anxiolytic-like behavioral, decrease in food intake, besides hyperlocomotion, which is a robust but not well understood phenomenon. Previous findings suggest that dopamine transmission plays a crucial role in NPS hyperactivity. Considering the close relationship between dopamine and Parkinson Disease (PD), and also that NPSR receptors are expressed on dopaminergic nuclei in the brain, the current study attempted to investigate the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of 6-OHDA and systemic administration of haloperidol. Motor deficits induced by 6-OHDA and haloperidol were evaluated on Swiss mice in the rota-rod and catalepsy test. Time on the rotating rod and time spent immobile in the elevated bar were measured respectively in each test. L-Dopa, a classic antiparkinsonian drug, and NPS were administrated in mice submitted to one of the animal models of PD related above. 6-OHDA injection evoked severe motor impairments in rota-rod test, while the cataleptic behavior of 6-OHDA injected mice was largely variable. The administration of L-Dopa (25 mg/kg) and NPS (0,1 and 1 nmol) reversed motor impairments induced by 6-OHDA in the rota-rod. Haloperidolinduced motor deficits on rota-rod and catalepsy tests which were reversed by L-Dopa (100 e 400 mg/kg), but not by NPS (0,1 and 1 nmol) administration. The association of L-Dopa 10 mg/kg and NPS 1 nmol was also unable to counteract haloperidol-induced motor deficits. To summarize, 6-OHDA-, but not haloperidol-, induced motor deficits were reversed by the central administration of NPS. These data suggest that NPS possibly facilitates dopamine release in basal ganglia, what would explain the overcome of motor performance promoted by NPS administration in animals pretreated with 6-OHDA, but not haloperidol. Finally, the presented findings point, for the first time, to the potential of NPSR agonist as an innovative treatment for PD.

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 da estimulação ambiental sobre os aspectos motores, cognitivos e neuronais em um modelo farmacológico progressivo da doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

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

Mudanças endógenas e suprafisiológicas nos níveis de estrógeno: efeitos sobre a amnésia induzida pela escopolamina em ratas intactas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Efeitos do substrato e da densidade populacional sobre as atividades comportamentais e níveis de homócitos em relação à densidade em Litopenaeus vannamei (BOONE, 1931)

Carciniculture in Brazil occupies world-wide prominence due to shrimp culture, and the state of Rio Grande do Norte has presented the best results in the culture of the Litopenaeus vannamei in the last decade. This species has been shown to adapt easily to different environments and is between the five most cultivated penaeids of the world. The ponds are usually constructed in areas close to water courses and estuaries. Stock density and substrate ponds can pollute environment, causing losses in the growth and survival of the shrimps, being considered stress factors. Shrimps in inadequate densities and substrates can result reduced productivity of the farm; and favor diseases. So, it is important to verify how these variables influence the development of the animals in the culture farms. Our objective was to study the influence of the type of substrate and the stock density on the behavior and haemocyte count of the L. vannamei. Individually marked juvenile shrimps were kept in aquaria with 30 L of seawater and continuous aeration, in 12L-12D photoperiod. They were observed through Ad libitum and focal sampling instantaneous methods during thirty days, five times per week, six times per day (8:00 to 18:00) in windows of 15 minutes every two hours. The marking of carapace permitted quantifying molting and the feeding was supplied three times a day. Two experiments were carried out: the first one tested animals in the three different substrates (fine sand, smaller rocks-SPP and biggest rocks-SGR) with 33 shrimp/m2. In the second one, the animals were tested in three stock densities (26, 52 and 66 shrimp/m2) in fine sand substrate. At the end of experiment, biometry (first and second ones) and haemocyte count (second one) were made. The behavior of the L. vannamei seems to have been influenced by substrate and stocking density. In low granulometry of the substrate; the exploratory behavior became more frequent and inactivity of the shrimps was reduced. Burrowing was registered in sand substrate, specially in the initial period of the day. Cleaning was gradually higher along the day, presenting the biggest levels as the dark phase approached. The ingestion of feeding was more frequent in low density, and the animals were bigger and heavier at the end of the experiment. In the fine sand condition, the animals presented better growth, probably associated with the burrowing. The molting was equivalent in all types of substrate, but it was more frequent in high densities. Mortality of the shrimps was more frequent in high densities, and cannibalism and diseases were also registered in that condition. The clinical signals were similar to the ones of infectious mionecrosis (IMNV), generally associated with environment and physical stress. The haemocyte count was low for the hematologic standards of the penaeid, which we attributed for greater dilution of haemolymph in the postmolting phase. Smaller shrimps presented lower levels of haemocytes in relation to the bigger animals, count was also low in 26 shrimp/m2 density. The study demonstrates that stocking density and the granulometry of the substrate can affect the welfare, the health and the behavior of the L. vannamei. The sand substrate and low stocking density can be important tools in the management systems of shrimp production