Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-13T20:44:53Z No. of bitstreams: 1 FladjanyEmanuellyFaustinoDaSilva_DISSERT.pdf: 1465669 bytes, checksum: 76f9e44b1ed2cc1d2970fdd63a651050 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-16T23:07:37Z (GMT) No. of bitstreams: 1 FladjanyEmanuellyFaustinoDaSilva_DISSERT.pdf: 1465669 bytes, checksum: 76f9e44b1ed2cc1d2970fdd63a651050 (MD5) / Made available in DSpace on 2017-02-16T23:07:37Z (GMT). No. of bitstreams: 1 FladjanyEmanuellyFaustinoDaSilva_DISSERT.pdf: 1465669 bytes, checksum: 76f9e44b1ed2cc1d2970fdd63a651050 (MD5) Previous issue date: 2016-08-05 / O medo e a ansiedade s?o emo??es adaptativas caracterizadas por um conjunto de altera??es fisiol?gicas e comportamentais que ocorrem quando os indiv?duos se sentem amea?ados fisicamente e/ou psicologicamente. Apesar dos comportamentos de medo e ansiedade serem caracter?sticos, estudo das ?ltimas duas d?cadas t?m mostrado que diferentes fontes de medo podem ativar diferentes vias neurais e que h? diferen?as entre medo condicionado (aprendido) e medo incondicionado (inato). As vias do medo condicionado envolvem o c?rtex frontal medial e os n?cleos central e basolateral da am?gdala, enquanto o medo de predador (inato) envolve o n?cleo medial da am?gdala e n?cleos da zona medial do hipot?lamo. Sabe-se que as fun??es encef?licas s?o coordenadas por sistemas de neurotransmissores e seus receptores que s?o expressos nas mais diversas regi?es do sistema nervoso, exercendo diferentes fun??es. O Neuropept?deo S (NPS) ? um neurotransmissor cujo estudos em roedores mostra sua import?ncia como regulador de ansiedade e vig?lia, reduzindo a ansiedade, aumentando a vig?lia e o comportamento locomotor, sendo ent?o um ansiol?tico e estimulante, o que o torna um potencial alvo para estudos farmacol?gicos e cl?nicos. Neste trabalho realizamos a inje??o intracerebroventricular (icv) de NPS em camundongos e mapeamento da express?o de Fos (prote?na indicadora de atividade celular) em n?cleos envolvidos nas vias de medo condicionado e incondicionado. A an?lise dos nossos resultados mostraram que a administra??o icv de NPS promoveu uma express?o de Fos diferenciada nos n?cleos central e basolateral da am?gdala, indicando um papel no medo condicionado. / Fear and anxiety are emotions featured by a group of physiological and behavioral changes that occur when subjects feel threatened physically and/or psychologically. For the last two decades many studies have showed that different sources of fear are able to activate different neural pathways, where conditioned (learned) and unconditioned (innate) fear run over different trails. The conditioned fear involves the frontal medial cortex and the central and basolateral nuclei of the amygdala, when the fear of predator (unconditioned) involves nuclei of the medial hypothalamus. It is known that the brain functions are coordinated by neurotransmitter's systems and its receptors that are expressed in many different places around the brain, having different functions. The Neuropeptide S (NPS) is a neurotransmitter whose studies have showed its important role as an anxiety and awake regulator. NPS decreases anxiety and increases awakeness and locomotor behavior, been thus an anxiolytic and stimulating neurotransmitter, what makes it a potential target for pharmacological and clinical studies. In the present work we injected NPS icv in mice and looked for the Fos-expressing neurons in the nuclei of the conditioned and unconditioned pathways. The analysis of our results showed that the icv NPS promoted the increase in Fos expression in the central and basolateral amygdala, what indicates its role in the conditioned fear.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2017-12-26T13:48:34Z No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-29T11:25:22Z (GMT) No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) / Made available in DSpace on 2017-12-29T11:48:08Z (GMT). No. of bitstreams: 1 CAROLINA_GARRIDO_ZINN_TES.pdf: 7131704 bytes, checksum: 554f552cadd232d7ef553c1f275476ba (MD5) Previous issue date: 2017-08-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The social recognition memory (SRM) is crucial to reproduction, formation of social groups and species survival. It is well known that oxytocin, vasopressin, sexual hormones and the olfactory bulb are strongly involved in the formation of SEM. Despite its relevance, the involvement of neurotransmitters such as dopamine (DA), noradrenaline (NE) and histamine (HIS), as well as the brain structures basolateral amygdala (BLA) and CA1 region of dorsal hippocampus ? commonly known for their importance in consolidating and maintaining other types of memories ? remains unknown when concerning SRM. Therefore, the first part of this study aims to evaluate the participation of the D1/D5 dopaminergic, ?-adrenergic and H2 histaminergic receptors into BLA and CA1 on consolidation of SRM. For this, male Wistar adult rats (3 months) were submitted to the social discrimination task (SDT), which is based on the natural tendency of the rodents to explore the novelty. The adult animal was exposed to a juvenile (21 days) conspecific for 1 hour (training session) and 24 hours later to the juvenile previously met (familiar) and to a new juvenile during 5 minutes (test session), when the exploration time was measured. Pharmacological interventions took place immediately after the training session. We verified that the H2 histaminergic receptors are required to the consolidation of SRM both in CA1 and BLA. However, the activation of D1/D5 dopaminergic and ?-adrenergic receptors interferes in an opposite way in the two brain structures: D1/D5 receptors are required in CA1, but not in BLA for consolidation of MRS, whereas activation of ?-adrenergic receptors is indispensable in BLA, but not in CA1. Methylphenidate (MPH) is a drug widely used in the treatment of Attention Deficit Hyperactivity Disorder. It exerts its therapeutic effect by increasing levels of DA and NE in brain structures involved in the learning processes, such as prefrontal cortex (PFC) and hippocampus. Since DA and NE have opposite actions in MRS, we decided to evaluate the effect of MPH on the formation and recall of MRS, since this drug acts on the levels of both neurotransmitters and has been used for academic doping by healthy individuals. Using SDT, with pharmacological interventions at different times, we verified that: 1) MPH, administered acutely prior to the information acquisition, blocked SRM; 2) Blockade was reversed when the animals received MPH at the time of acquisition and retrieval, characterizing the phenomenon known as state dependency (SD) learning; 3) The SD is associated to the CPF, but not to CA1; 4) SD does not depend on CA1, since the increase of NE in CA1 impairs the retrieval of the SRM. In addition, we verified that the 21-day chronic treatment with MPH causes a greater persistence of MRS when a weaker training session is performed. Considering the obtained results, this work demonstrates that the hippocampus, the basolateral amygdala and the prefrontal cortex, modulated by the dopaminergic and noradrenergic systems, regulate the SRM processing. / A mem?ria de reconhecimento social (MRS) ? crucial ? reprodu??o, forma??o de grupos sociais e sobreviv?ncia das esp?cies. Sabe-se que a ocitocina, a vasopressina, os horm?nios sexuais e o bulbo olfat?rio t?m um forte envolvimento na forma??o da MRS. Apesar de sua relev?ncia, a participa??o de neurotransmissores, como dopamina (DA), noradrenalina (NA) e histamina (HIS), bem como das estruturas am?gdala basolateral (BLA) e regi?o CA1 do hipocampo (CA1) ? j? amplamente conhecidos pela sua import?ncia na consolida??o e manuten??o de outros tipos de mem?rias ? permanece desconhecido quanto ? MRS. Sendo assim, a primeira parte deste trabalho buscou avaliar a participa??o dos receptores D1/D5 dopamin?rgicos, ?-adren?rgicos e H2 histamin?rgicos na BLA e CA1 sobre a consolida??o da MRS. Para isso, ratos Wistar machos adultos (3 meses) foram submetidos a tarefa de discrimina??o social (TDS), que baseia-se na tend?ncia natural dos roedores de explorar a novidade. O animal adulto foi exposto a um juvenil (21 dias) coespec?fico por 1 hora (sess?o de treino) e 24 horas depois ao juvenil previamente encontrado (familiar) e a um novo juvenil durante 5 minutos (sess?o de teste), quando o tempo de explora??o foi medido. As interven??es farmacol?gicas ocorreram imediatamente ap?s a sess?o de treino. Verificou-se que os receptores H2 histamin?rgicos s?o necess?rios para a consolida??o da mem?ria tanto em CA1 quanto na BLA. Contudo a ativa??o dos receptores D1/D5 dopamin?rgicos e ?-adren?rgicos interfere de forma oposta nas duas estruturas cerebrais: os receptores D1/D5 s?o necess?rios em CA1, mas n?o na BLA para a consolida??o da MRS, enquanto a ativa??o dos receptores ?adren?rgicos ? indispens?vel na BLA, por?m n?o em CA1. O metilfenidato (MPH) ? um f?rmaco amplamente utilizado no tratamento do Transtorno do D?ficit de Aten??o e Hiperatividade. Exerce seu efeito terap?utico pelo aumento nos n?veis de DA e NA em estruturas cerebrais envolvidas nos processos de aprendizagem, como c?rtex pr?frontal (CPF) e hipocampo. Uma vez que a DA e a NA tem a??es opostas na MRS, decidimos avaliar o efeito do MPH sobre a forma??o e a evoca??o da MRS, j? que esta droga atua sobre os n?veis de ambos os neurotransmissores e tem sido utilizada como doping acad?mico por indiv?duos saud?veis. Utilizando a TDS, com as interven??es farmacol?gicas em diferentes momentos, verificamos que: 1) o MPH, administrado de forma sist?mica aguda previamente ? aquisi??o da informa??o, bloqueou a MRS; 2) O bloqueio foi revertido quando os animais receberam MPH no momento da aquisi??o e da evoca??o, caracterizando o fen?meno conhecido como depend?ncia de estado (DE); 3) A DE ? associada ao CPF, mas n?o a CA1; 4) A DE n?o depende de CA1, pois o aumento de NA em CA1 prejudica a evoca??o da MRS. Al?m disso, verificamos que o tratamento cr?nico de 21 dias com MPH causa uma maior persist?ncia da MRS, quando realizada uma sess?o de treino mais fraca. Considerando os resultados obtidos, este trabalho demonstra que o hipocampo, a am?gdala basolateral e o c?rtex pr?-frontal, modulados pelos sistemas dopamin?rgico e noradren?rgico, regulam o processamento da MRS.

Made available in DSpace on 2014-12-17T15:37:14Z (GMT). No. of bitstreams: 1 LuaneMSF_DISSERT.pdf: 1389510 bytes, checksum: 8552b7721296822725c28f11de3be41a (MD5) Previous issue date: 2012-07-30 / GABAergic neurotransmission has been implicated in many aspects of learning and memory, as well as mood and anxiety disorders. The amygdala has been one of the major focuses in this area, given its essential role in modulating emotionally relevant memories. However, studies with male subjects are still predominant in the field. Here we investigated the consequences for an aversive memory of enhancing or decreasing GABAergic transmission in the basolateral nucleus of the amygdala (BLA). Wistar female rats were trained in the plus-maze discriminative avoidance task, in which they had to learn to avoid one of the enclosed arms where an aversive stimulus consisting of a bright light and a loud noise was given (day 1). Fifteen minutes before the test session (day 2) animals received 0,2 μL infusions of either saline solution, the GABAergic agonist muscimol (0,05 mg/ml), or the GABAergic antagonist bicuculine (0,025 mg/ml) bilaterally intra-BLA. On the test day, females in proestrous or estrous presented adequate retrieval and did not extinguish the task, while females in metestrous or diestrous presented impaired retrieval. In the first group, muscimol infusion impaired retrieval and bicuculline had no effect, suggesting naturally low levels of GABAergic transmission in the BLA of proestrous and estrous females. In the second group, muscimol infusion had no effect and bicuculline reversed retrieval impairment, suggesting naturally high levels of GABAergic transmission in the BLA of metestrous and diestous females. Additionally, proestrous and estrous females presented higher anxiety levels compared to metestrous and diestrous females, which could explain better performance of this group. On the other hand, BLA GABAergic system did not interfere with the innate fear response because drug infusions had no effect in anxiety. Thus, retrieval alterations caused by the GABAergic drugs were probably related specifically to memory processes / A transmiss?o GABA?rgica est? envolvida em diversos aspectos do aprendizado e da mem?ria, assim com em transtornos de humor e ansiedade. Um dos grandes focos nessa ?rea tem sido a am?gdala, uma estrutura essencial para a modula??o de mem?rias emocionais. Entretanto, os estudos na ?rea s?o majoritariamente feitos em machos. Nesse trabalho foi investigado em ratas as consequ?ncias de uma transmiss?o GABA?rgica aumentada ou reduzida na am?gdala basolateral (BLA) para uma mem?ria aversiva. Ratas Wistar foram treinadas na esquiva discriminativa no labirinto em cruz elevado, aprendendo a evitar um dos bra?os fechados, onde recebiam um est?mulo aversivo consistindo de uma luz forte e um som alto (dia 1). Quinze minutos antes do teste (dia 2) os animais receberam 0,2μL de solu??o salina, do agonista GABA?rgico muscimol (0,05 mg/ml), ou do antagonista GABA?rgico bicuculina (0,025 mg/ml) bilateralmente intra-BLA. F?meas testadas em proestro e estro evocaram adequadamente e n?o extinguiram a tarefa, enquanto f?meas testadas em metaestro e diestro tiveram um d?ficit na evoca??o. No primeiro grupo, a infus?o de muscimol prejudicou a evoca??o e a infus?o de bicuculina n?o teve efeito, indicando n?veis naturalmente baixos de transmiss?o GABA?rgica na BLA de f?meas em proestro e estro. J? no segundo grupo, a infus?o de muscimol n?o teve efeito e a infus?o de bicuculina reverteu o d?ficit na evoca??o, indicando n?veis naturalmente altos de transmiss?o GABA?rgica na BLA de f?meas em metaestro e diestro. F?meas em proestro e estro apresentaram maiores n?veis de ansiedade quando comparadas ?s f?meas em metaestro e diestro, o qu? poderia explicar o melhor desempenho desse grupo. Entretanto, o sistema GABA?rgico da BLA provavelmente n?o interfere com o medo inato, uma vez que os f?rmacos n?o tiveram efeito na ansiedade. Dessa forma, as altera??es na evoca??o causadas por eles parecem estar relacionadas especificamente a processos mnem?nicos