Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-13T20:11:13Z No. of bitstreams: 1 BarbaraThaiseDaSilvaFreire_DISSERT.pdf: 2117227 bytes, checksum: ea3ed2322a685c0dbab26e3132b6aeee (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-15T23:55:52Z (GMT) No. of bitstreams: 1 BarbaraThaiseDaSilvaFreire_DISSERT.pdf: 2117227 bytes, checksum: ea3ed2322a685c0dbab26e3132b6aeee (MD5) / Made available in DSpace on 2017-02-15T23:55:52Z (GMT). No. of bitstreams: 1 BarbaraThaiseDaSilvaFreire_DISSERT.pdf: 2117227 bytes, checksum: ea3ed2322a685c0dbab26e3132b6aeee (MD5) Previous issue date: 2016-07-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O envolvimento de receptores do tipo 5-HT3, assim como a rela??o do N?cleo Dorsal da Rafe na modula??o da ansiedade vem sendo citados na literatura. Levando em considera??o a grande parcela da popula??o que ? afetada pelos transtornos de ansiedade, torna-se imprescind?vel a procura por novas formas de tratamento mais eficientes e pelo aumento do conhecimento acerca do assunto. Nesse sentido, o objetivo do presente estudo ? testar a hip?tese de que receptores do tipo 5-HT3 presentes na por??o dorsal do n?cleo dorsal da rafe (NDR) modulem as respostas relacionadas ? ansiedade em ratas. No experimento 1, ratas Wistar com ? 90 dias de idade receberam tratamento (v.o) de ondansetrona na dose de 0,1, 1 e 10 mg/kg/mL e, 60 minutos ap?s, foram submetidas ao teste do Labirinto em T Elevado (LTE). 24 horas ap?s o LTE, os animais receberam novamente a ondansetrona e foram submetidas ao teste do Campo Aberto. Nos experimentos 2 e 3, as ratas foram submetidas ? cirurgia estereot?xica para implanta??o de c?nula intra-NDR e receberam administra??o local de salina ou dolasetrona nas doses de 100, 500 e 1000nmol (experimento 2) ou salina ou mCPBG nas doses de 2,5, 5 e 10?g (experimento 3). Em ambos, 5 minutos ap?s a infus?o com a droga, os animais foram submetidos ao teste do LTE, e 24 horas ap?s, receberam infus?o e foram submetidos ao teste do Campo Aberto para obten??o de curvas doseresposta. A ondansetrona na dose de 10mg/Kg/mL aumentou a lat?ncia de fuga no LTE, sugerindo um efeito do tipo panicol?tico. A dolasetrona n?o promoveu nenhum efeito no teste do LTE, em nenhuma das doses testadas. J? o agonista mCPBG em todas as doses aumentou a lat?ncia de esquiva inibit?ria em todas as tentativas, sugerindo um efeito do tipo ansiog?nico. Os resultados obtidos no teste do Campo Aberto mostrou que n?o houve altera??o na atividade locomotora das ratas causada pelos tratamentos. Os dados obtidos refor?am a import?ncia dos receptores 5-HT3 no NDR na modula??o da ansiedade. / The involvement of both 5-HT3 receptors and dorsal raphe nucleus in the modulation of anxiety has been presented in the literature. Considering that most of population is affected by anxiety disorders, it is essential to search for new and more efficient forms of treatment and to increase the knowledge on the subject. The aim of this study is to test the hypothesis that the 5-HT3 receptors in the dorsal part of the dorsal raphe nucleus (dNDR) modulates the responses related to anxiety in rats. In experiment one, female Wistar rats with ? 90 days old were treated (p.o.) with ondansetron at doses of 0.1, 1 and 10 mg/kg/mL and 60 minutes later, were submitted to the elevated T maze (ETM) test. 24 hours later, they received ondansetron and were submitted to the open Field Test. In the experiments 2 and 3, the rats were submitted to the stereotactic surgery for implantation of intra-NDR cannula and received administration (via infusion) of saline or dolasetron at doses of 100, 500 and 1000nmol (experiment 2) or saline or mCPBG at doses of 2.5, 5 and 10mg (experiment 3). In both experiments, 5 minutes after the infusion of the drug, the animals were submitted to the test of ETM, and 24 hours after, they received drug infusion and were submitted to the open field test, to obtain dose-response curves. Ondansetron at a dose of 10mg/kg/mL increased latency of escape response in ETM, suggesting an panicolytic-like effect. The dolasetron caused no effect in ETM test in any of the tested doses. The agonist mCPBG instead, increased the inhibitory avoidance latency in all doses, suggesting an anxiogenic-like effect. Data obtained in the open field test showed no change in locomotor activity of rats following the treatments. The data here obtained supports the importance of 5-HT3 receptors in the NDR in the modulation of anxiety.

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.