Submitted by Matheus Fitipaldi Batistela null (matheusbatistela@gmail.com) on 2018-04-04T21:32:10Z No. of bitstreams: 1 Dissertação Mestrado e Artigo - Matheus Fitipaldi Batistela.pdf: 5209326 bytes, checksum: 0a1d08ad10c8c4629fb067e1907fe0e2 (MD5) / Approved for entry into archive by Maria Luiza Carpi Semeghini (luiza@assis.unesp.br) on 2018-04-05T17:13:29Z (GMT) No. of bitstreams: 1 batistela_mf_me_assis.pdf: 5209326 bytes, checksum: 0a1d08ad10c8c4629fb067e1907fe0e2 (MD5) / Made available in DSpace on 2018-04-05T17:13:30Z (GMT). No. of bitstreams: 1 batistela_mf_me_assis.pdf: 5209326 bytes, checksum: 0a1d08ad10c8c4629fb067e1907fe0e2 (MD5) Previous issue date: 2018-03-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Deakin e Graeff propuseram que ansiedade e o pânico seriam regulados pela serotonina ou 5-hidroxitriptamina (5-HT), possuindo mais de um mecanismo de controle. Ambos os mecanismos têm sua origem nos núcleos Dorsal da Rafe (NDR) e Mediano da Rafe (NMR). O NDR possui ainda, cinco diferentes subnúcleos ao longo do eixo rostrocaudal: dorsal (DRD), ventral (DRV), lateral/asas laterais (lwDR), caudal (DRC) e interfascicular (DRI), sendo que os subnúcleos DRC, DRD e DRI originam a via modulatória do transtorno de ansiedade generalizada e o subnúcleo lwDR origina a via modulatória do transtorno do pânico. Sabe-se que as mulheres são mais suscetíveis à manifestação dos transtornos de ansiedade e de pânico do que os homens. Estudos com modelos animais de ansiedade mostram que nas fases do ciclo hormonal onde ocorre maior liberação de estrógeno, proestro e estro, é constatada ansiólise. De maneira oposta em animais na fase de metaestro e diestro, nas quais há baixa concentração sérica de estradiol, os comportamentos defensivos observados apontam para o aumento da ansiedade. Receptores para estrógeno, alfa (ERα) e beta (ERβ), foram encontrados em estruturas encefálicas descritas por Deakin e Graeff como relacionadas com a manifestação dos transtornos de ansiedade e co-localizadas em receptores serotonérgicos. Assim, esse estudo teve por objetivo avaliar a expressão de neurônios serotonérgicos e não-serotonérgicos no NMR e nos diferentes subnúcleos do NDR em relação a fase do ciclo estral de ratas e após a ovariectomia bilateral. As fêmeas foram perfundidas e os encéfalos foram processados a fim de se realizar o processo de imunohistoquímica de dupla-marcação para a proteína c-Fos (marcador indireto de ativação celular) e da enzima triptofano hidroxilase (TPH – presente somente em neurônios serotonérgicos). Não se constatou qualquer diferença quando se analisou o NMR. Os resultados encontrados mostraram um maior número de neurônios serotonérgicos e não-serotonérgicos ativados na fase de proestro, principalmente nos subnúcleos Dorsal (DRD) e Caudal (DRC). Enquanto que na fase de diestro e após ovariectomia bilateral os resultados apontaram um menor número na expressão de TPH nos subnúcleos DRD, Ventral (DRV) e DRC. Os resultados encontrados são compatíveis com achados anteriores que indicam que os subnúcleos dorsal e caudal são responsáveis pela modulação de comportamentos defensivos relacionados à ansiedade. Como houve diferença na ativação das estruturas ao longo do ciclo estral conclui-se que a presença de hormônios sexuais, principalmente o estradiol, é responsável por essas alterações observadas. / Deakin and Graeff proposed that anxiety and panic would be regulated by serotonin or 5-hydroxytryptamine (5-HT), having more than one control mechanism. Both mechanisms have their origin in Dorsal Raphe Nucleus (DRN) and Median Raphe Nucleus (MRN). The DRN also has five sub-regions along the rostrocaudal axis: dorsal (DRD), ventral (DRV), lateral / lateral wings (lwDR), caudal (DRC) and interfascicular (DRI), being that the DRC, DRD and DRI subnuclei originate the modulatory pathway of generalized anxiety disorder and the subnucleus lwDR originates the modulatory pathway of panic disorder. It is known that women are more susceptible to the manifestation of anxiety and panic disorders than men. Studies with animal models of anxiety show that in the phases of the hormonal cycle where estrogen release occurs, like proestrus and estrous, anxiolysis is observed. On the other hand, animals in the metaestrus and diestrus phase, in which there is a low concentration of estradiol, the observed defensive behaviors point to an increase in anxiety. Receptors for estrogen, alpha (ERα) and beta (ERβ) were found in structures described by Deakin and Graeff as re lated to a manifestation of anxiety disorders and co-localized in serotonergic receptors. Thus, this study aimed to evaluate the expression of serotonergic and non-serotonergic neurons in the MRN and in the different NDR subnuclei in relation to the phases of estrous cycle of rats and after a bilateral ovariectomy. The females were perfused and the brains were processed in order to perform the double-label immunohistochemistry process for c-Fos protein (cellular activation indirect marker) and tryptophan hydroxylase (TPH - present only in serotonergic neurons). No difference was found when MRN was analyzed. The results showed a higher number of serotonergic and non-serotonergic neurons activated in the proestrus phase, mainly in the Dorsal (DRD) and Caudal (DRC) subnuclei. While in the late diestrus phase and after bilateral ovariectomy the results indicated a lower number of TPH expression in the sub-nuclei DRD, Ventral (DRV) and DRC. The results are compatible with previous findings that have shown the responsible of dorsal and caudal subnuclei in the modulation of defensive behaviors related to anxiety. As there was a difference in the activation of the structures during the estrous cycle it was concluded that the presence of sex hormones, mainly estradiol, is responsible for these observed changes

Les changements de forme et les mouvements des cellules constituant les tissus relèvent de la morphogenèse épithéliale. Dans les tissus segmentés les compartiments antérieurs et postérieurs représentent des domaines morphogénétiques indépendants constitués de lignées cellulaires distinctes et séparées par des barrières biophysiques. Le laboratoire a montré que lors de la fermeture dorsale de l’embryon de drosophile, certaines cellules des segments centraux de l’ectoderme, appelées « Cellules Mixer » (CMs), sont reprogrammées pour traverser la frontière segmentale dans un phénomène qui prend le nom de « mixing ». La reprogrammation des CMs est JNK dépendante induisant l’expression de novo du gène engrailed (en). La mise au point de nouveaux outils génétiques a permis de révéler le rôle de deux familles de gènes impliqués dans les mécanismes de reprogrammation et de mixing : le gène Polycomb (Pc) et les gènes Hox. La technique de DNA-FISH, qui analyse l’interaction entre Pc et le PRE d’en, a ainsi montré que la voie JNK induit l’expression de novo d’en par dé-répression de l’activité Pc dans les CMs. De manière intéressante l’analyse approfondie des mutants Pc a dévoilé que les gènes Hox abdominal-A (abdA) et Abdominal-B (AbdB) contrôlent le domaine du mixing. Des expériences de gain et perte de fonction ont par la suite confirmé le rôle positif d’abdA et le rôle négatif d’AbdB dans le mixing. En conclusion, l’ensemble des résultats obtenus ont permis de dévoiler la présence d’un réseau génétique composé de par JNK, en, Pc et les gènes Hox contrôlant les mécanismes de reprogrammation cellulaire et de remodelage des frontières segmentales au cours du développement normal. / Tissue morphogenesis relies on patterned cell shape changes and movements taking place in specific morphogenetic domains. In segmented tissues, anterior and posterior compartments represent independent morphogenetic domains which are made of distinct lineages separated by boundaries. We previously reported on a rare event leading to the exchange of specific ‘Mixer Cells’ (MCs) between compartments of the ectoderm. During dorsal closure, MCs, which are of anterior origin, cross the boundary to integrate the adjacent posterior compartment through de novo expression of the posterior determinant Engrailed (En). This reprograming process is dependent on JNK signalling and is restricted to the central abdominal region. Here, we show that JNK signalling represses Polycomb (Pc) expression and that loss of Pc leads to an absence of MCs reprogramming. FISH-DNA coupled to immunostaining further shows that MCs fate transition is accompanied by a release of the en promoter from the repressing Pc bodies. Interestingly, our genetic data reveal that spatial control of MCs reprograming depends on the activity of the Hox genes abdominal-A (abdA) and Abdominal-B (AbdB). In their respective domains, abd-A promotes mixing while abd-B behaves as a strong repressor, thus restricting cell mixing to the central abdominal region. Together, these results provide new insights into the mechanisms of developmental reprogramming, showing that segment boundary plasticity relies on regional control of cell remodelling involving a gene regulatory network composed of JNK, en, Pc, and Hox activities.

Understanding how memory is formed requires looking beyond the genes involved to the neural circuitry and temporal aspects of memory. In this dissertation I have focused my investigation on Dorsal Paired Medial (DPM) neurons, two modulatory neurons essential for memory in Drosophila. DPM neurons highly express the amnesiac (amn) gene, which encodes for a putative pre-pro-neuropeptide. amn function in DPM neurons is required for memory. Here I provide evidence that DPM neurons are cholinergic and that acetylcholine (ACh) and AMN act as co-transmitters essential for DPM function. In order to investigate the temporal requirements of DPM output I blocked transmitter release during discrete intervals in the memory process using shibirets1 and tested flies for shock and sugar-reinforced memory. These experiments demonstrated that stable memory requires persistent transmitter release from DPM neurons. Furthermore these results suggest AMN and DPM neurons act as general stabilizers of mushroom body dependent memory. To further investigate the neural circuitry underlying DPM function I disrupted DPM projections onto the mushroom body lobes by ectopically expressing DScam17-2::GFP in DPM neurons. Flies with DPM neurons that predominantly project to the mushroom body α´/β´ lobes exhibit normal memory, and blocking transmitter release from the mushroom body prime lobes neurons themselves abolishes memory indicating DPM neuron-mushroom body α´/β´ neuron interaction that are critical for memory. Taken together, the experimental evidence presented here are used to provide a rudimentary model of the neural circuitry involved in memory stability, where DPM neurons form a recurrent feedback loop with the mushroom body α´/β´ lobe neurons and act to stabilize odorspecific conditioned memories at Kenyon cell synapses.

abstract: The present study explores the role of motion in the perception of form from dynamic occlusion, employing color to help isolate the contributions of both visual pathways. Although the cells that respond to color cues in the environment usually feed into the ventral stream, humans can perceive motion based on chromatic cues. The current study was designed to use grey, green, and red stimuli to successively limit the amount of information available to the dorsal stream pathway, while providing roughly equal information to the ventral system. Twenty-one participants identified shapes that were presented in grey, green, and red and were defined by dynamic occlusion. The shapes were then presented again in a static condition where the maximum occlusions were presented as before, but without motion. Results showed an interaction between the motion and static conditions in that when the speed of presentation increased, performance in the motion conditions became significantly less accurate than in the static conditions. The grey and green motion conditions crossed static performance at the same point, whereas the red motion condition crossed at a much slower speed. These data are consistent with a model of neural processing in which the main visual systems share information. Moreover, they support the notion that presenting stimuli in specific colors may help isolate perceptual pathways for scientific investigation. Given the potential for chromatic cues to target specific visual systems in the performance of dynamic object recognition, exploring these perceptual parameters may help our understanding of human visual processing. / Dissertation/Thesis / M.A. Psychology 2011

Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-20Bitstream added on 2014-06-13T18:29:07Z : No. of bitstreams: 1 pires_rb_me_botfm.pdf: 268409 bytes, checksum: a7f99374144af3decea275454b7e5df4 (MD5) / A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta mortalidade apesar do melhor entendimento de sua fisiopatologia e avanços no tratamento. A Ventilação Oscilatória de Alta Frequência (VOAF) é método protetor por utilizar baixos volumes correntes (VC). Existem terapias adjuvantes à ventilação, dentre as quais se destaca a posição prona, que possibilita homogeneização da distribuição do VC e promove recrutamento alveolar. O objetivo foi investigar o efeito da posição prona associada à VOAF sobre a oxigenação, inflamação, histologia e dano oxidativo pulmonares, comparando-a com a posição supina neste mesmo modo ventilatório em modelo experimental de lesão pulmonar aguda (LPA) induzida em coelhos. Trinta coelhos foram instrumentados com traqueostomia e acessos vasculares e ventilados. A LPA foi induzida por infusão traqueal de salina aquecida (30mL/Kg, 38°C). Os coelhos foram submetidos à VOAF e divididos em dois grupos (n=15), um ventilado em posição supina (GS) e outro em posição prona (GP). VOAF foi iniciada com pressão aérea média de 16 cmH2O, que foi diminuída a cada 30 minutos até 10-11 cmH2O. Nos últimos 30 minutos os coelhos foram reposicionados em posição supina. Parâmetros ventilatórios e hemodinâmicos foram registrados a cada 30 minutos durante 150 minutos. Os desfechos foram: oxigenação, avaliada pela relação PaO2/FiO2 e índice de oxigenação (IO); inflamação pulmonar, avaliada pela porcentagem de polimorfonucleares (PMN) no lavado broncoalveolar (BAL) e pelo nível de TNF-alfa medido no BAL e no tecido pulmonar nas áreas ventral e dorsal; estresse oxidativo tecidual pulmonar, determinado pelo método de peroxidação lipídica (malondialdeído); e lesão tecidual pulmonar, determinada por escore histológico de lesão por área pulmonar. O nível de significância avaliado... / Acute respiratory distress syndrome (ARDS) has been associated to high mortality rate despite better understanding of its pathophysiology and advances in treatment. High-frequency oscillatory ventilation (HFOV) is a protective ventilatory method because of using low tidal volume (VT). There are also many adjunctive therapies, of which prone position is known to allow homogenization of VT distribution and to promote alveolar recruitment. The objective was to investigate the prone position and HFOV association effects on oxygenation, inflammation, oxidative damage and lung histology, comparing to the supine position in this same ventilation mode, in experimental acute lung injury (ALI) induced in rabbits. Thirty rabbits were instrumented with tracheotomy and vascular catheters and ventilated. ALI was induced by tracheal infusion of warm saline (30mL/Kg, 38°C). Rabbits were submitted to HFOV and divided in two groups (n=15), one ventilated in supine position (SG), and the other in prone position (PG). HFOV was initiated with mean airway pressure of 16 cmH2O, which was decreased each 30 minutes until 10-11 cmH2O. In the last 30 minutes, all rabbits were repositioned to supine position. Ventilatory and hemodynamic parameters were recorded every 30 minutes for 150 minutes. The outcomes were: oxygenation, measured by PaO2/FiO2 ratio and oxygenation index (OI); lung inflammation, assessed by the percentage of polymorphonuclear cells (PMN) in bronchoalveolar lavage fluid (BAL) and by the level of TNF- alpha measured in BAL and in lung tissue, in ventral and dorsal areas; lung tissue oxidative stress, determined by the method of lipid peroxidation (malondialdehyde); and lung tissue damage, as determined by a histological score of injury, in each lung area. A significance level of 5% was... (Complete abstract click electronic access below)

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-22T23:19:52Z No. of bitstreams: 1 RalinyOliveiraSantos_DISSERT.pdf: 9138081 bytes, checksum: 38a641e3ede8b16533d07f1b59d2e852 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-26T19:19:40Z (GMT) No. of bitstreams: 1 RalinyOliveiraSantos_DISSERT.pdf: 9138081 bytes, checksum: 38a641e3ede8b16533d07f1b59d2e852 (MD5) / Made available in DSpace on 2016-02-26T19:19:40Z (GMT). No. of bitstreams: 1 RalinyOliveiraSantos_DISSERT.pdf: 9138081 bytes, checksum: 38a641e3ede8b16533d07f1b59d2e852 (MD5) Previous issue date: 2014-08-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Indiv?duos dependentes de etanol, ao reduzirem ou cessarem seu consumo, apresentam um conjunto de sinais e sintomas, dentre eles, alguns relacionados ? ansiedade. Para um melhor entendimento das bases neurais envolvidas com a ansiedade na abstin?ncia, ensaios pr?-cl?nicos v?m utilizando modelos de consumo de etanol seguido de retirada em ratos submetidos a distintos testes de ansiedade, dentre eles, o labirinto em cruz elevado. O presente estudo teve por objetivo investigar se a retirada do etanol em curto e longo prazo promoveria altera??es comportamentais sugestivas de ansiedade no teste do labirinto em cruz elevado (LCE) e no teste do campo aberto (CA) e, ainda, se influenciaria o n?mero de c?lulas imunorreativas para a serotonina (5-HT-IR) no n?cleo dorsal da rafe (NDR), fonte de inerva??o seroton?rgica ascendente relacionada ? ansiedade. Ratas Wistar com aproximadamente 90 dias de vida foram submetidas a concentra??es crescentes de etanol como ?nica fonte de dieta l?quida (2% durante os tr?s primeiros dias, seguido de 4% durante tr?s dias e 6% durante 15 dias) ou ?gua (grupo controle), ambos com livre acesso ? ra??o. Na etapa comportamental, no 21? dia de consumo, o etanol foi substitu?do por ?gua (retirada) e, ap?s 72 horas ou 21 dias de retirada, os animais controle e submetidos ? retirada foram expostos ao teste do LCE, onde foram avaliadas as porcentagens de tempo gasto e de entradas nos bra?os abertos e o n?mero de entradas nos bra?os fechados durante 5 minutos. Vinte e quatro horas ap?s o teste no LCE, os animais foram submetidos ao teste do CA por 15 minutos. Durante este per?odo avaliou-se a dist?ncia total percorrida pelos animais e durante os 5 minutos iniciais foram avaliados o tempo, a dist?ncia e o n?mero de entradas no centro do aparato. Na etapa imunoistoqu?mica, os enc?falos de animais submetidos ao consumo de etanol por 21 dias, seguidos ou n?o de retirada de 72 horas e 21 dias, e seus controles foram submetidos ? t?cnica da imunoistoqu?mica para detectar c?lulas 5-HT-IR nas por??es dorsal e caudal do NDR. Os dados comportamentais mostraram que tanto a retirada do etanol em curto prazo, quanto em longo prazo diminuiu a explora??o dos bra?os abertos do LCE. No teste do CA n?o foram observadas altera??es na locomo??o no per?odo de 15 minutos; por?m, no mesmo teste, durante os 5 primeiros minutos observou-se efeito do tipo ansiog?nico nos animais submetidos ? 22 dias de retirada do etanol. Na etapa imunoistoqu?mica, n?o foram observadas diferen?as na contagem de c?lulas 5-HTIR nas por??es dorsal e caudal do NDR dos animais submetidos ? retirada em curto e longo prazo do etanol, em rela??o ao controle. No entanto, o consumo do etanol por 21 dias reduziu a contagem de c?lulas 5-HT-IR na regi?o dorsal deste n?cleo. Em conjunto, os dados aqui obtidos demonstram um efeito do tipo ansiog?nico promovido pela retirada em curto e longo prazo do etanol n?o relacionado a altera??es na marca??o de serotonina nas por??es dorsal e caudal do NDR. / Ethanol withdrawn individuals present a wealth of signs and symptoms, some of them related with anxiety. To better understand brain areas involved in anxiety caused by ethanol abstinence, preclinical studies have been employing models of ethanol consumption followed by withdrawal in rodents submitted to behavioral tests of anxiety, such as the elevated plus-maze. The aim of this study was to investigate if short- or long-term ethanol withdrawal could alter both anxiety-related behaviors in the elevated plus-maze (EPM) and open field tests and the number of serotonin immunorreactive cels in the dorsal raphe nucleus, a midbrain area associated with anxiety. Female Wistar rats (90 days old) were submitted to increasing concentrations of ethanol (2% for 3 days, 4% for 3 days and 6% for 15 days) as the only source of liquid diet and the control group received water ad libitum. Both groups received food ad libitum. In the behavioral experiments, on 21st day of consumption, ethanol was substituted by water (withdrawal) and 72 h or 21 days after withdrawal animals were submitted to the EPM, where it was evaluated the percentage of time and entries in the open arms and the entries in the enclosed arms during 5 minutes. Twenty and four hours after testing in the EPM, animals were submitted to the open field test for 15 minutes, where the distance traveled by the animals was observed along this period. During the first 5 minutes, the distance traveled, entries and time spent in the center of the test were analyzed. In the immunohistochemistry study, animals were submitted to 21 days of consumption of ethanol followed or not by 72 hours and 21 days of withdrawal previously perfusion, brain tissue preparation and quantification of serotonin dyed cells in the dorsal and caudal portions in the dorsal raphe nucleus. Behavioral data showed that both short- and long-term ethanol withdrawals reduced the open arms exploration in the EPM. In the open field test there were no locomotor activity changes during the total 15 minutes; however, longterm ethanol withdrawal reduced the exploration in the center of the open field during the first 5 minutes. In the immunohistochemistry step, there were no differences, when short- and long-term withdrawn groups were compared with control group; nevertheless, the chronic consumption of ethanol decreased the number of serotonergic immunorreactive cells in the dorsal part of dorsal raphe nucleus. Taken together, results here obtained suggest that both short- and long-term ethanol withdrawals promoted an anxiogenic-like effect that was not related with changes in the serotonin immunorreactivity in the dorsal and caudal parts of the dorsal raphe nucleus.

O transtorno do pânico (TP) é um transtorno de ansiedade caracterizado por ataques de pânico recorrentes e inesperados, com um prognóstico crônico. Entre as drogas utilizadas no tratamento do TP, os benzodiazepínicos (BZs) de alta potência, como o alprazolam e o clonazepam, apresentam a vantagem de serem eficazes logo no início do tratamento. Assim como outras drogas BZs, tais como o diazepam e o flurazepam, estes compostos também são empregados como ansiolíticos no tratamento de pacientes com transtorno de ansiedade generalizada. O mecanismo da ação primária dessas drogas ocorre pela interação com os sítios de ligação BZs presentes nos receptores do ácido gama-aminobutírico do tipo A (GABAA), facilitando a neutotransmissão GABAérgica. Entretanto, ainda permanecem desconhecidos os substratos neurais envolvidos no efeito panicolítico causado pelos BZs. Dentre os substratos em potencial, a substância cinzenta periaquedutal dorsal (SCPD), uma estrutura mesencefálica criticamente relacionada à fisiopatogênica do TP, apresenta alta densidade de receptores GABAA e de sítios de ligação BZs. Neste trabalho avaliamos o envolvimento do complexo receptor GABAA/BZ presente na SCPD no efeito panicolítico promovido pela administração sistêmica de alprazolam em ratos Wistar. Para isso, empregamos o labirinto em T elevado (LTE), que além da resposta de fuga, que é associada ao pânico, também permite avaliar a resposta de esquiva inibitória, associada à ansiedade. Neste modelo, o alprazolam inibe a expressão da resposta de fuga, indicando efeito panicolítico e inibe a aquisição da esquiva inibitória, sugestivo de efeito ansiolítico. Além do LTE, também empregamos os modelos experimentais da hipóxia e o de Vogel, associados ao pânico e a ansiedade, respectivamente. Os resultados obtidos mostraram que o efeito panicolítico promovido pela administração sistêmica de alprazolam, observado na resposta de fuga do LTE, foi bloqueado pela administração intra-SCPD de flumazenil, antagonista dos sítios de ligação BZs, ou de bicuculina, antagonista dos receptores 10 GABAA. No teste da hipóxia, o efeito panicolítico causado pela administração sistêmica de alprazolam foi inibido, porém não significativamente bloqueado, pela administração intra-SCPD de bicuculina. Já o efeito ansiolítico, observado na resposta de esquiva do LTE e no teste do beber punido de Vogel, não foi bloqueado pela administração intra-SCPD de flumazenil ou de bicuculina. No conjunto, nossos resultados sugerem que o complexo receptor GABAA/BZ da SCPD está envolvido no efeito panicolítico, mas não ansiolítico, promovido pela administração sistêmica de alprazolam. / Panic Disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks with a chronic prognosis. Among the drugs used to treat PD, highpotency benzodiazepines (BZs), such as alprazolam and clonazepam, have the advantage of causing significant effects early in the treatment. Like others BZs, such as diazepam and flurazepam, these compounds are also used as anxiolytics in the treatment of patients with generalized anxiety disorder. The primary mechanism of action of these drugs is the interaction with BZs binding sites present at gammaaminobutyric acid type A receptors (GABAA), facilitating GABAergic neurotransmission. However, it remains yet unknown the neural substrates involved in the panicolytic-like action caused by BZs. Among the potential substrates, the dorsal periaqueductal gray matter (DPAG), a mesencephalic structure critically associated with the physiopathology of PD, presents a high density of GABAA receptors and of BZs binding sites. In this work, we evaluated the participation of the GABAA/BZ receptor complex present in the DPAG in the panicolytic-like effect caused by systemic administration of alprazolam in Wistar rats. For this, we use the elevated T-maze (ETM), that besides the escape response which is associated with panic, also allows the measurement of inhibitory avoidance acquisition, which has been related to anxiety. In this model, alprazolam inhibits the expression of escape, indicating a panicolytic-like effect and inhibits the acquisition of inhibitory avoidance, suggestive of an anxiolytic effect. In addition to the ETM, animals were also tested in the hypoxia and Vogel\'s conflict tests, which have been associated with panic and anxiety, respectively. The results showed that the panicolytic-like effect caused by alprazolam in ETM\'s escape response was blocked by intra-DPAG injection of flumazenil, a BZs binding site antagonist, or bicuculline, a GABAA receptor antagonist. In the hypoxia test, the panicolytic-like effect caused by alprazolam was inhibited, but not significantly blocked, by intra-DPAG injection of bicuculline. The anxiolytic effect observed in the 12 ETM\'s avoidance task or in the Vogel\'s conflict test was not blocked by intra-DPAG injection of flumazenil or bicuculline. Taken together, our results suggest that the GABAA/BZ receptor complex located in the DPAG is involved in the panicolytic, but not anxiolytic, effect caused by systemic administration of alprazolam.

Este trabalho objetivou avaliar através do exame clínico, radiográfico e ultra-sonográfico a articulação fêmuro-tíbio-patelar pós desmotomia patelar medial. Foram utilizados oito equinos, machos e fêmeas, de peso, raça e idade variáveis. Todos animais foram submetidos a desmotomia patelar medial no membro pélvico direito. Os exames clínico e ultra-sonográfico foram realizados no 7º, 14º, 21º, 28º, 43º, 58º, 88º e 118º dia do pós-operatório. Os exames radiográficos e do líquido sinovial foram realizados no 15º, 30º, 60º, 90º e 120º dia do pós-operatório. No pós-operatório foi observado durante exame radiográfico do joelho direito, aumento do ângulo entre a superfície articular proximal da patela e a superfície cranial distal do fêmur, formação óssea na crista tibial, entesofitos na patela, deslocamento da patela e irregularidade óssea na superfície patelar lateral. No exame ultra-sonográfico foi observado aumento da espessura (p<0,05) no segmento proximal e médio do ligamento patelar intermédio do membro pélvico direito, desmite do patelar intermédio, enteseofitos na patela, distensão do recesso articular medial do fêmur, efusão articular e irregularidade da cartilagem do sulco troclear femoral. Conclui-se que a desmotomia patelar medial causa alterações no joelho devido a instbilidade articular e deve ser indicada apenas nos casos que não responderam a outras forma de tratamento. / This study aimed the evaluation of the femurotibiopatellar joint trough clinical, radiographic and ultrasonographic examinations after experimental medial patellar desmotomy. Medial patellar desmotomy was performed on the right hindlimb in eight mixed-breed horses. The clinical and ultrasonographic evaluation was performed on day 7, 14, 21, 28, 43, 58, 88 e 118 after surgery. The radiographic and synovial fluid evaluation was performed on day 15, 30, 60, 90 e 120 after surgery. It was observed during radiographic evaluation of the right stifle, an increase of the angle between the patellar proximal articular surface and the cranial distal femur surface. During ultrasonographic evaluation it was observed thickening (p<0,05) on the proximal and midlle segment of the midlle patellar ligament on the right hindlimb, entesophyte at the patella, femoral medial joint recess distending, joint effusion and cartilage irregularity of the femoral troclear groove. The medial patellar desmotomy causes stifle changes and must be performed only in animals non responsive to other treatment.

O medo e a ansiedade são emoções que apresentam claro valor adaptativo, e que tem suas origens nas reações de defesa que os animais exibem em resposta a situações de ameaça que podem comprometer sua integridade física ou sobrevivência. Recentes estudos têm indicado que a matéria cinzenta periaquedutal dorsal (MCPD) está envolvida na organização e expressão de comportamentos intempestivos do tipo fuga e luta, os quais são relacionados ao estado de medo, e também participa, juntamente com estruturas prosencefálicas (ex. córtex pré-frontal, sistema septo-hipocampal e amígdala), do controle de comportamentos defensivos mais elaborados e orientados relacionados à ansiedade. O presente estudo investigou a participação da MCPD na modulação de diferentes comportamentos defensivos (p. ex. fuga, esquiva e avaliação de risco) induzidos por métodos artificial (estimulação química) e naturalístico (exposição ao predador) em camundongos. Na primeira etapa, investigamos o padrão de resposta comportamental induzida pela infusão do ácido D,L-homocistéico (DLH, estímulo aversivo químico) na MCPD em diferentes situações ou ambientes, com e sem grande disponibilidade de espaço - o Mouse Defense Test Battery (MDTB) e a Arena (Experimento 1), respectivamente. Além disso, o presente estudo avaliou a habilidade dos animais de reagirem a estímulos aversivos (predador) durante o período inicial (nos 60 s iniciais) do efeito do ácido DLH (fuga explosiva) (Experimento 3), e imediatamente após esse período, no qual o animal apresente comportamento de congelamento ou imobilidade (Experimento 2). Nossos resultados indicaram que a fuga desencadeada pela estimulação química é a resposta predominante de camundongos e que sua exibição depende da disponibilidade de espaço, uma vez que a maioria dos saltos observados na arena está intimamente relacionada ao contato tátil do animal com as paredes do aparato. Esse perfil de respostas de fuga explosiva e saltos parece não representar o padrão comportamental defensivo natural, tal como acontece diante de uma ameaça proximal (ex. um predador), uma vez que durante a estimulação química os camundongos apresentaram um déficit na estratégia antipredador. A segunda etapa do estudo avaliou os efeitos da injeção intra-MCPD do agonista glutamatérgico ácido N-metil-D-aspártico (NMDA), do inibidor da enzima de síntese do óxido nítrico neuronial (NOSn), N?-propil-L-arginina (NPLA) (Experimento 4), e do agonista não seletivo de receptores do fator de liberação de corticotrofina (CRF), CRF ovino (oCRF) (Experimento 5), no comportamento defensivo de camundongos submetidos ao MDTB e ao teste de exposição ao rato (Rat Exposure Test; RET). Os resultados da segunda etapa demonstraram que a ativação de receptores NMDA na MCPD de camundongos intensifica comportamentos relacionados à esquiva do predador. De maneira interessante, essas alterações produzidas pelo NMDA foram consistentemente revertidas pelo inibidor da NOSn, previamente microinjetado no mesmo sítio. Além disso, efeitos intrínsecos do NPLA atenuaram as respostas de esquiva e de avaliação de risco em camundongos submetidos ao RET. Por fim, os resultados da segunda etapa também apontaram para um efeito proaversivo (nas respostas de salto e de esquiva) do agonista de receptores CRF, indicando uma participação dos sistemas glutamatérgico, nitrérgico e CRFérgico, localizados na MCPD, na modulação de diferentes estratégias defensivas (ex. esquiva, avaliação de risco e saltos) de camundongos submetidos ao confronto com o predador. Em conjunto, nossos resultados corroboram a hipótese de que a MPCD está envolvida tanto na organização e expressão de comportamentos intempestivos do tipo fuga e luta como também no controle de comportamentos defensivos mais elaborados e orientados, tais como a avaliação de risco e a esquiva. / The midbrain dorsal periaqueductal grey (DPAG) is part of the brain defensive system involved in active defense reactions to threatening stimuli. Many lines of evidence suggest that besides fundamentally controlling fear-like responses (fight and flight) the DPAG also controls responses related to anxiety, such as avoidance and risk assessment. This study investigated the role of DPAG on different defensive strategies (i.e. flight, avoidance and risk assessment) elicited by artificial (chemical stimulation, Experiments 1-3) and naturalistic (exposure to predator, Experiments 4 and 5) paradigms in mice. Firstly, D,L-Homocysteic acid (DLH) was infused into the DPAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber and a large oval runway, the Mouse Defense Test Battery (MDTB) apparatus (Exp. 1). We also investigated the ability of mice to react to a threatening stimulus (ex. a predator) during (Exp. 3) and immediately after (Exp. 2) the hyperactive responses (ex. jumping and running) induced by DLH injection. Our results indicated that running as opposed to jumping is the primary response in mice injected with DLH into the DPAG when the environment enables flight. However, mice did not react the predator during the flight reaction induced by chemical stimulation, suggesting the behavioral profile induced by DLH infusion into the DPAG is not related to a normal antipredator flight. In the Experiments 4 and 5, we evaluated the effects of three different compounds, N-methyl-D-Aspartate (NMDA), a NMDA receptor agonist, N?-propyl-L-arginine (NPLA), an neuronal nitric oxide synthase (nNOS) inhibitor as well as ovine CRF (oCRF), a nonspecific corticotropin-releasing factor (CRF) receptor agonist, injected into the DPAG of mice, in two predator-stress situations, the Mouse Defense Test Battery (MDTB), and the Rat Exposure Test (RET). Firstly, our results demonstrated that NMDA receptor activation into the mouse DPAG enhances antipredator reactivity (avoidance), an effect that was attenuated by prior infusion of NPLA into the same site. Moreover, the results from the Experiment 4 indicated that the NPLA treatment per se induces consistent anti-aversive effects on defensive behaviors (avoidance and risk assessment) of mice confronted by predator. Finally, our results pointed out a proaversive effect (e.g. increased jump escapes and avoidance behaviors) following intra-DPAG infusion of oCRF, suggesting an important role of glutamatergic, nitrergic and CRFergic systems into the DPAG on the defensive behaviors (risk assessment, avoidance and jumps) elicited by the confront to the predator. Taken together, present results are compatible with previous studies which have emphasized the role of the periaqueductal gray in the modulation of behavioral responses related to anxiety such as risk assessment and avoidance besides fundamentally controlling fear-like responses.

Les antidépresseurs ont un effet antiallodynique qui dépend de la stimulation des récepteurs β2-adrénergiques. Ceux-ci stimulent la production d’adénosine monophosphate cyclique (AMPc) régulé par les phosphodiestérases de type 4 (PDE4). Nous avons ici étudié l’effet d’inhibiteurs de PDE (iPDE) sur la douleur neuropathique, grâce à des approches de pharmacologie comportementale chez la souris complétées par de l’imagerie calcium et des approches moléculaires. Nos résultats montrent un effet antiallodynique des iPDE4 et des iPDE5. L’action des iPDE4 est liée à une diminution d’expression du TNFα dans le ganglion rachidien et au recrutement des récepteurs delta des opioïdes. Celle des iPDE5 nécessite à la fois les récepteurs mu et delta. Nous montrons aussi que l’action d’un iPDE4 dépend de la dose, l’activation de cellules gliales semblant corrélée à l’effet antiallodynique à faible dose, alors que celle des neurones à forte dose a un effet pronociceptif via les récepteurs TRPV1. / Antidepressants have an antiallodynic action that is dependent on β2-adrenoceptor stimulation. These receptors stimulate the cAMP production, which is regulated by type 4 phosphodiesterases (PDE4). Here, we studied that action of PDE inhibitors (iPDE) on neuropathic pain, using behavioral pharmacology approaches in mice, completed by calcium imaging and molecular approaches. Our results show the iPDE4s and iPDE5s have an antiallodynic action. The iPDE4s act through a decreased expression of TNFα in dorsal root ganglia and the recruitment of the delta opioid receptors. The action of iPDE5 requires both mu and delta opioid receptors. We also show that the action of an iPDE4 depends on the dose, the activation of glial cells at low dose being correlated with an antiallodynic action, while the recruitment of neurons at higher doses has a pronociceptive action via TRPV1 receptors.