Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Avaliação comportamental e neuroquímica de ratos em dessincronização forçada: possíveis implicações para um modelo animal de oscilações no humor

Bipolar disorder has been growing in several countries. It is a disease with high mortality and has been responsible by the social isolation of the patients. Bipolar patients have alterations in circadian timing system, showing a phase shift in various physiological variables. There are several arguments demonstrating alterations in circadian rhythms may be part of the bipolar disorder pathophysiology. Given the necessity for further elucidation, the goal of this study was to validate the forced desynchronization protocol as an animal model for bipolar disorder. To do this, Wistar rats were submitted to a forced desynchronization protocol which consists in a symmetrical light dark cycle with 22h. Under this protocol, rats dissociate the locomotor activity rhythm into two components: one synchronized to the light / dark cycle with 22h, and another component with period longer than 24 hours following the animal endogenous period. These rhythms with different periods sometimes there is coincidence, which we named CAP (Coincidence Active Phase) and the opposite phase, non-coincidence, called NCAP (Non-Concidence Active Phase). The hypothesis is that in CAP animals present a mania-like behavior and animals in NCAP depressive-like behavior. We found some evidence described in detail throughout this thesis. In sum, the animals under forced desynchronization protocol were more stressed, showed an increase in stereotypic behaviors such as grooming and reduction in other behaviors such as risk assessment and vertical exploration when compared to the control group. The CAP animals showed increased locomotor activity, especially during the dark phase when compared to controls (rats under T24) and less depressive behavior in the forced swim test. The animals in NCAP showed a higher anxiety in elevated plus maze, but they don t have ahnedonia. The animals under dissociation have more labeled 5HT1A cells at the amygdala area, which appoint that they have more amygdala inhibition. Taking these data together, we could partially validated the forced desynchronization protocol as an animal model for mood oscillations

Caracterização do ritmo de atividade/repouso do Mocó (Kerodon Rupestris) em fotoperíodo artificial

Kerodon rupestris (rock cavy, mocó) is an endemic caviidae of Brazilian northeast that inhabits rocky places in the semi arid region. The aim of this study was to characterize the activity/rest rhythm of the rock cavy under 12:12 h LD cycle and continuous light. In the first stage, seven animals were submitted to two light intensities (LD; 250:0 lux and 400:0 lux; 40 days each intensity). In the second stage four males were kept for 40 days in LD (470:<1 lux), for 18 days in LL 470 lux (LL470) and for 23 days in red dim light below 1 lux (LL<1). In the third stage three males were initially kept in LD 12:12 h (450:<1 lux) and after that in LL with gradual increase in light intensity each 21 days (<1 lux LL<1; 10 lux-LL10; 160 lux LL160; 450 lux LL450). In the fourth stage it was analyzed the motor activity of 16 animals in the first 10 days in LD. Motor activity was continuously recorded by passive infrared movement sensors connected to a computer and totaled in 5 min bins. The activity showed circadian and ultradian rhythms and activity peaks at phase transitions. The activity and the rest occurred in the light as well as in the dark phase, with activity mean greater in the light phase for most of the animals. The light intensity influenced the activity/rest rhythm in the first three stages and in the first stage the activity in 400 lux increased in four animals and decreases in two. In the second stage, the tau for 3 animals in LL470 was greater than 24 h; in LL<1 it was greater than 24 h for one and lower for two. In the third stage the tau decreased with the light intensity increase for animal 8. During the first days in the experimental room, the animals did not synchronize to the LD cycle with activity and rest occurring in both phases. The results indicate that the activity/rest rhythm of Kerodon rupestris can be affected by light intensity and that the synchronization to the LD cycle results from entrainment as well as masking probably as a consequence of the action of two or more oscillators with low coupling strength

Estudo da preferência manual durante o desenvolvimento ontogenético em sagüi comum ( Callithix jacchus)

The study of manual preference is a widely used approach to investigate cerebral laterality in nonhuman primates. However, in New World primates, little is known about the ontogenesis of hand use asymmetry, in both forced and spontaneous activities, as well as how they correlate with sexual hormones. Accordingly, a longitudinal study was conducted on the manual preference of 6 female and 4 male common marmosets (Callithrix jacchus). The study included the record of forced tests to reach for the food using only one hand (forced activity) and activities such as grooming (auto and social), scratching, grasping the food and hanging, in weekly sessions from the infantile (4 months) to the early adult phase (15 months). Feces samples were also collected, at least once a week, to evaluate the level of gonadal steroids and their influence on these behaviors. In the forced activity, the results confirm the influence of the development period on manual preference during feeding, shown by the increase in lateral stability when grasping the food between the juvenile and adult phases. During this period, a sexual hormone effect on development was also observed, mainly of progesterone in females and androgen in males, but no difference between sexes was found. In the females, progesterone also influenced the manual preference index, with a proportional increase in the degree of manual asymmetry during puberty. With respect to spontaneous activities, the animals showed proportional use of both hands when scratching, hanging, holding the food and grooming. A positive correlation was also found between the preference for holding the food in forced activities and in spontaneous activities

Influência de fotoperíodo artificial no comportamento de um primata neotropical diurno (Callithrix jacchus)

One of the main environmental cues for the adjustment of temporal organization of the animals is the light-dark cycle (LD), which undergoes changes in phase duration throughout the seasons. Photoperiod signaling by melatonin in mammals allows behavioral changes along the year, as in the activity-rest cycle, in mood states and in cognitive performance. The aim of this study was to investigate if common marmoset (Callithrix jacchus) exhibits behavioral changes under short and long photoperiods in a 24h cycle, assessing their individual behaviors, vocal repertoire, exploratory activity (EA), recognition memory (RM) and the circadian rhythm of locomotor activity (CRA). Eight adult marmosets were exposed to a light-dark cycle of 12:12; LD 08:16; LD 12:12 and LD 16:08, sequentially, for four weeks in each condition. Locomotor activity was recorded 24h/day by passive infrared motion detectors above the individual cages. A video camera system was programmed to record each animal, twice a week, on the first two light hours. From the videos, frequency of behaviors was registered as anxiety-like, grooming, alert, hanging position, staying in nest box and feeding using continuous focal animal sampling method. Simultaneously, the calls emitted in the experimental room were recorded by a single microphone centrally located and categorized as affiliative (whirr, chirp), contact (phee), long distance (loud shrill), agonistic (twitter) and alarm (tsik, seep, see). EA was assessed on the third hour after lights onset on the last week of each condition. In a first session, marmosets were exposed to one unfamiliar object during 15 min and 24h later, on the second session, a novel object was added to evaluate RM. Results showed that long days caused a decreased of amplitude and period variance of the CRA, but not short days. Short days decreased the total daily activity and active phase duration. On long days, active phase duration increased due to an advance of activity onset in relation to symmetric days. However, not all subjects started the activity earlier on long days. The activity offset was similar to symmetric days for the majority of marmosets. Results of EA showed that RM was not affected by short or long days, and that the marmosets exhibited a decreased in duration of EA on long days. Frequency and type of calls and frequency of anxiety-like behaviors, staying in nest box and grooming were lower on the first two light hours on long days. Considering the whole active phase of marmosets as we elucidate the results of vocalizations and behaviors, it is possible that these changes in the first two light hours are due to the shifting of temporal distribution of marmoset activities, since some animals did not advance the activity onset on long days. Consequently, the marmosets mean decreased because the sampling was not possible. In conclusion, marmosets synchronized the CRA to the tested photoperiods and as the phase angle varied a lot among marmosets it is suggested that they can use different strategies. Also, long days had an effect on activity-rest cycle and exploratory behaviors

Desenvolvimento dos filhotes de atobas-de-pés-vermelhos (Sula sula) no aquipélego de Fernando de Noronha/PE

Parental care s costs increase with the time spent due to incapacity of parents give assistance to increasing offspring food s requirement. This parental care deficits is crucial to offspring s emancipation that involve abilities development to they survive independently. In this work we observe 16 Red-footed boobies chick (Sula sula) on different stages of development, at area of Parque Nacional Marinho of Fernando de Noronha s archipelago, from August to October of 2005. Our data show the parents presence decrease during chick development and an activity frequency modification, in move and fly, which suggest the emancipation s chick development. We observe also the action of Kleptoparasits and the influence with offspring parental care. Our data show consistency with the literature. However, we consider that studies carried through during the peak of the reproductive station can support the hypothesis of that the conflicts, together with the initial period of development of the flight, can be representative in terms of mortality of chicks for the studied species

Desenvolvimento formal de aplicações para smartcards

Smart card applications represent a growing market. Usually this kind of application manipulate and store critical information that requires some level of security, such as financial or confidential information. The quality and trustworthiness of smart card software can be improved through a rigorous development process that embraces formal techniques of software engineering. In this work we propose the BSmart method, a specialization of the B formal method dedicated to the development of smart card Java Card applications. The method describes how a Java Card application can be generated from a B refinement process of its formal abstract specification. The development is supported by a set of tools, which automates the generation of some required refinements and the translation to Java Card client (host) and server (applet) applications. With respect to verification, the method development process was formalized and verified in the B method, using the Atelier B tool [Cle12a]. We emphasize that the Java Card application is translated from the last stage of refinement, named implementation. This translation process was specified in ASF+SDF [BKV08], describing the grammar of both languages (SDF) and the code transformations through rewrite rules (ASF). This specification was an important support during the translator development and contributes to the tool documentation. We also emphasize the KitSmart library [Dut06, San12], an essential component of BSmart, containing models of all 93 classes/interfaces of Java Card API 2:2:2, of Java/Java Card data types and machines that can be useful for the specifier, but are not part of the standard Java Card library. In other to validate the method, its tool support and the KitSmart, we developed an electronic passport application following the BSmart method. We believe that the results reached in this work contribute to Java Card development, allowing the generation of complete (client and server components), and less subject to errors, Java Card applications.

BSmart: desenvolvimento rigoroso de aplicações Java Card com base no método formal B

Java Card technology allows the development and execution of small applications embedded in smart cards. A Java Card application is composed of an external card client and of an application in the card that implements the services available to the client by means of an Application Programming Interface (API). Usually, these applications manipulate and store important information, such as cash and confidential data of their owners. Thus, it is necessary to adopt rigor on developing a smart card application to improve its quality and trustworthiness. The use of formal methods on the development of these applications is a way to reach these quality requirements. The B method is one of the many formal methods for system specification. The development in B starts with the functional specification of the system, continues with the application of some optional refinements to the specification and, from the last level of refinement, it is possible to generate code for some programming language. The B formalism has a good tool support and its application to Java Card is adequate since the specification and development of APIs is one of the major applications of B. The BSmart method proposed here aims to promote the rigorous development of Java Card applications up to the generation of its code, based on the refinement of its formal specification described in the B notation. This development is supported by the BSmart tool, that is composed of some programs that automate each stage of the method; and by a library of B modules and Java Card classes that model primitive types, essential Java Card API classes and reusable data structures

Modelagem e desenvolvimento de um banco de dados geográficos : aplicação à elaboração de mapas de sensibilidade ambiental ao derramamento de óleo na área costeira entre galinhos e São Bento do Norte-RN

The area between Galinhos and São Bento do Norte beaches, located in the northern coast of the Rio Grande do Norte State is submitted to intense and constant processes of littoral and aeolian transport, causing erosion, alterations in the sediments balance and modifications in the shoreline. Beyond these natural factors, the human interference is huge in the surroundings due to the Guamaré Petroliferous Pole nearby, the greater terrestrial oil producing in Brazil. Before all these characteristics had been organized MAMBMARE and MARPETRO projects with the main objective to execute the geo-environmental monitoring of coastal areas on the northern portion of RN. There is a bulky amount of database from the study area such as geologic and geophysical multitemporal data, hydrodynamic measurements, remote sensing multitemporal images, thematic maps, among others; it is of extreme importance to elaborate a Geographic Database (GD), one of the main components of a Geographic Information System (GIS), to store this amount of information, allowing the access to researchers and users. The first part of this work consisted to elaborate a GD to store the data of the area between Galinhos and São Bento do Norte cities. The main goal was to use the potentiality of the GIS as a tool to support decisions in the environmental monitoring of this region, a valuable target for oil exploration, salt companies and shrimp farms. The collected data was stored as a virtual library to assist men decisions from the results presented as digital thematic maps, tables and reports, useful as source of data in the preventive planning and as guidelines to the future research themes both on regional and local context. The second stage of this work consisted on elaborate the Oil-Spill Environmental Sensitivity Maps. These maps based on the Environmental Sensitivity Index Maps to Oil Spill developed by the Ministry of Environment are cartographic products that supply full information to the decision making, contingency planning and assessment in case of an oil spilling incident in any area. They represent the sensitivity of the areas related to oil spilling, through basic data such as geology, geomorphology, oceanographic, social-economic and biology. Some parameters, as hydrodynamic data, sampling data, coastal type, declivity of the beach face, types of resources in risk (biologic, economic, human or cultural) and the land use of the area are some of the essential information used on the environmental sensitivity maps elaboration. Thus using the available data were possible to develop sensitivity maps of the study area on different dates (June/2000 and December/2000) and to perceive that there was a difference on the sensitivity index generated. The area on December presented more sensible to the oil than the June one because hydrodynamic data (wave and tide energy) allowed a faster natural cleaning on June. The use of the GIS on sensitivity maps showed to be a powerful tool, since it was possible to manipulate geographic data with correctness and to elaborate more accurate maps with a higher level of detail to the study area. This presented an medium index (3 to 4) to the long shore and a high index (10) to the mangrove areas highly vulnerable to oil spill

Influência do tipo de abrigo e da frequência de oferta alimentar no comportamento do camarão Macrobrachium rosenbergii (De Man 1879)

Macrobrachium rosenbergii is a freshwater prawn which presents agonistic behavior and heterogeneous growth. It is known that captive conditions can intensify agonism causing injuries and decreased survival, generating a condition of poor welfare. Based on this, we aim to investigate the behavior of M. rosenbergii in the juvenile phase according to different types of shelter and frequencies of feed offer, emphasizing their agonistic behavior. For this, juveniles were observed in the laboratory in three steps. At step I we characterized the behavioral profile; prawns were kept in eight aquariums (27 prawns/m2 ), identified and observed four times along both phases of 24 h light cycle. At step II (2 experiments), we evaluated the use of shelters (brick or polyethylene rolls) and their influence on agonism by the animals. For classification of animals in dominance rank, the method used was David's Score. At step III (3 experiments), we evaluated different frequencies of feed offer on the behavior of individuals, in particular agonism. Results showed that juveniles do not present a pattern activity/inactivity between the phases of the light cycle. We identified a dominance hierarchy among individuals taking advantage of access to food by the dominant, which showed greater weight gain although the frequency of intake did not differ between individuals. The type of shelter influenced the behavior of animals. Brick shelter generated a higher frequency of permanence and a reduction in the frequency of agonistic interactions. The distribution of food more frequently throughout the day, decreased the motivation of animals for food, as well as to fight. Prawns fed four times showed lower frequency of feed intake and agonistic interactions. Thus, we conclude the shelters which reduce animal’s detection by coespecifics and offer the food four times along the day reduce agonistic behavior. This result causes na improvement in life quality of the prawns and also in its quality as final product.

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Decisões comportamentais em contexto de forrageamento de dinoponera quadriceps

The behavioral decisions of animals do not occur randomly, because behaviors are adjusted to ensure the survival and reproduction of the animal. In this research, I examined behavioral decisions in the foraging context of the ant Dinoponera quadriceps with regard to orientation, food avaliation and foraging dynamic to individual level. The study was conducted at the Laboratory of Behavioral Biology at UFRN and in an area of secondary Atlantic Forest in FLONA-ICMBio Nísia Floresta/RN. In all observations and experiments, ants were marked individually with an alphanumeric code label fixed on the thorax. In the first part of the study, I analyzed the orientation cues used by D. quadriceps. The tests were performed in a maze of 17 compartments. Each forager was tested for 10 min in three sessions for six different treatments. The treatments consisted of the presence or absence of odor and superior or frontal visual cues. The workers demonstrated that the presence of odor is indispensable and front visual cues are more effective than superior visual cues. In the second part, I investigated the discrimination of food, considering the parameters, size, weight and volume. In a 'cafeteria' experiment, I offered cylindrical pieces of food (mortadella) in a Petri dish, within an experimental arena 1m². Initially, the pieces were of four different sizes; in a second step, the pieces were of the same size but with different weight; in the last step, the pieces had the same weight but different volumes. The results showed the effect of the size and weight parameters for food choice. In the third part of the study, I evaluated the influence of the activity of active foragers on inactive ones. In this part, the colonies were observed in a natural environment. The observations took place on three consecutive days in 10 episodes, total of 30 days for each colony, 12 hours/day. On the first day, I registered the output and input of workers; on the second day, the most active ants on the first day were taken and given back at the end of the observations; on the third day, the observations were similar to the first day. As a result, the workers of D. quadriceps show autostimulation and they do not show social facilitation and the colony compensates the absence of the most active workers. Based on the stated, I conclude that workers of D. quadriceps use chemical, frontal and superior visual orientation cues during their displacements. They discriminate the chosen food by size and weight. The regulation of activity dynamics of foragers is by autostimulation, an active worker does not influence the activity of an inactive worker, the successful search previous is the stimulus to the successful worker itself to continue foraging activity.

Desenvolvimento de novos biolubrificantes hidráulicos derivados dos óleos de maracujá e de moringa in natura e epoxidados

With the increasing environmental awareness, maximizing biodegradability and minimizing ecotoxicity is the main driving force for new technological developments. Thus, can be developed new biodegradable lubricants for use in environmentally sensitive areas. The aim of this study was to obtain new bio-lubricants from passion fruit (Passiflora edulis Sims f. flavicarpa Degener) and moringa (Moringa oleifera Lamarck) epoxidized oils and develop a new additive package using experimental design for their use as a hydraulic fluid. In the first stage of this work was performed the optimization of the epoxidation process of the oils using fractional experimental design 24-1 , varying the temperature, reaction time, ratio of formic acid and hydrogen peroxide. In the second step was investigated the selectivity, thermodynamics and kinetics of the reaction for obtaining the two epoxides at 30, 50 and 70 °C. The result of the experimental design confirmed that the epoxidation of passion fruit oil requires 2 hours of reaction, 50 °C and a ratio H2O2/C=C/HCOOH (1:1:1). For moringa oil were required 2 hours reaction, 50 °C and a ratio of H2O2/C=C/HCOOH (1:1:1.5). The results of the final conversions were equal to 83.09% (± 0.3) for passion fruit oil epoxide and 91.02 (±0,4) for moringa oil epoxide. Following was made the 23 factorial design to evaluate which are the best concentrations of corrosion inhibitor and anti-wear (IC), antioxidant (BHA) and extreme pressure (EP) additives. The bio-lubricants obtained in this step were characterized according to DIN 51524 (Part 2 HLP) and DIN 51517 (Part 3 CLP) standards. The epoxidation process of the oils was able to improve the oxidative stability and reduce the total acid number, when compared to the in natura oils. Moreover, the epoxidized oils best solubilized additives, resulting in increased performance as a lubricant. In terms of physicochemical performance, the best lubricant fluid was the epoxidized moringa oil with additives (EMO-ADI), followed by the epoxidized passion fruit oil with additives (EPF-ADI) and, finally, the passion fruit in natura oil without additives (PFO). Lastly, was made the investigation of the tribological behavior under conditions of boundary lubrication for these lubricants. The tribological performance of the developed lubricants was analyzed on a HFRR equipment (High Frequency Reciprocating Rig) and the coefficient of friction, which occurs during the contact and the formation of the lubricating film, was measured. The wear was evaluated through optical microscopy and scanning electron microscopy (SEM). The results showed that the addition of extreme pressure (EP) and anti-wear and corrosion inhibitor (CI) additives significantly improve the tribological properties of the fluids. In all assays, was formed a lubricating film that is responsible for reducing the coefficient of metal-to-metal wear. It was observed that the addition of EP and IC additives in the in natura vegetable oils of passion fruit and moringa did not favor a significant reduction in wear. The bio-lubricants developed from passion fruit and moringa oils modified via epoxidation presented satisfactory tribological properties and shown to be potential lubricants for replacement of commercial mineral-based fluids.

Aplicação do planejamento de experimentos no processo de desenvolvimento de produtos: pesquisa em uma sorveteria artesanal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

Padronização de testes para avaliação do estado de mania e potencial anti-maníaco de um agonista do receptor NOP

Bipolar disorder is characterized by mood impairment, alternating between mania/hypomania and depression, and its exact pathophysiology is already unknown. The treatment of bipolar disorder is based on prevention of the manic and depressive episodes using mood stabilizers. Nociceptin/orfanin FQ (N/OFQ) is an endogenous heptadecapeptide which binds as an agonist to NOP receptor, which is a G-coupled inhibitory receptor. N/OFQ and its receptor modulate a lot of functions in the organism, including emotional processes. It is known that the plasmatic concentration of N/OFQ is altered in patients in both phases depressive and manic of bipolar disorder and it is assumed that this system has a role on the etiology of this disorder. Concerning mania, the animal models used in research tend to focus in an unique aspect of the manic behavior, as hyperactivity or agressivity. In the 60’s, the hole board test was proposed, and it consists of an apparatus with holes where a behavior known as head-dippings is measured. High levels of head-dippings are suggestive of neophilia, while low levels can be characteristic of an anxious-like behavior. As the increase of exploratory and goal-directed behavior are characteristics of manic behavior, this test could help in mania research. Thus, this work was organized in 3 steps and aims to: (1) investigate the induction of a manic-like state promoted by ouabain, a Na+/K+-ATPase inhibitor, in the mouse open field test; (2) set up the hole board as a test to measure manic-like behaviors; and (3) investigate the N/OFQ effects in prevention of this kind of behavior on hole board. Male Swiss mice were used in this study, and they take part of only one of the described steps. Depending on the step performed, mice received one or more of the following treatments: (1) ouabain 10-6 , 10-5 , 10-4 , 10-3 or 10-2 M, intracerebroventricular (icv); (2) sodium valproate 300 mg/kg, intraperitoneal (ip); (3) sodium valproate 400 mg/kg, ip; (4) diazepam 1 mg/kg, ip; (5) methylphenidate 10 mg/kg, ip; and (6) N/OFQ 0,1 or 1 nmol, icv. The results suggest that hole board can be used to evaluate a manic state, through analysis of different animal behaviors. However, it was not possible to standard the model of Na+ /K+ -ATPase dysfunction through ouabain administration in mice. Moreover, the data suggest that N/OFQ, at the doses tested, has not affected the methylphenidate-induced mania-like behavior. Taken together, the results point to a new approach of manic research, through the hole board using. However, more studies are necessary in order to verify the role of N/OFQ system on bipolar disorder.