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Previous issue date: 2017-04-27 / Nociceptina-orfanina FQ (N/OFQ) ? um heptadecapept?deo, que atua como ligante end?geno do receptor NOP. O receptor NOP tem ampla express?o no sistema nervoso e sua ativa??o induz efeitos inibit?rios, causando redu??o da libera??o de neurotransmissores e/ou inibi??o do disparo neuronal, dependendo do s?tio (pr? ou p?s-sin?ptico) no qual ? expresso. Estudos in vivo t?m demonstrado o envolvimento do sistema N/OFQ-receptor NOP na modula??o dos estados emocionais. Este estudo visou avaliar os efeitos do agonista NOP, Ro65-6570, sobre as altera??es comportamentais de camundongos submetidos a uma situa??o de estresse incontrol?vel. Para tanto, foi utilizado o modelo do desamparo aprendido (DA), que emprega eletrochoques, incontrol?veis e imprevis?veis, nas patas dos animais como evento estressor para induzir um fen?tipo do tipo desamparado, que consiste num d?ficit do comportamento de escape do compartimento eletrificado. Nem todos os animais expostos ao DA desenvolvem o fen?tipo do tipo desamparado, logo, dois grupos distintos foram observados: camundongos desamparados e n?o-desamparados. Ap?s a exposi??o ao DA, foram realizados testes para observar as altera??es comportamentais que o estresse causou, como labirinto em cruz elevado (LCE), nata??o for?ada e campo aberto. Foi observado efeito ansiog?nico do DA nos camundongos desamparados, com diminui??o no n?mero de entradas e tempo gasto nos bra?os abertos do LCE, quando comparados aos grupos n?o-desamparados e naive. Ap?s essa etapa, foi avaliada a a??o do diazepam (1 mg/kg, via i.p.) e do agonista NOP, Ro65-6570 (1 mg/kg, via i.p.), no comportamento do tipo ansioso dos animais desamparados, bem como em sua locomo??o. O diazepam foi capaz de reverter o comportamento do tipo ansioso observado no teste do LCE pelos camundongos desamparados, sem preju?zo na locomo??o dos animais. De forma similar, a administra??o de Ro65-6570 tamb?m apresentou efeito ansiol?tico somente nos camundongos desamparados, sem afetar a atividade locomotora. Em conclus?o, este estudo aponta o sistema da N/OFQ-receptor NOP como um alvo terap?utico inovador para o tratamento de transtornos psiqui?tricos relacionados ao estresse. / Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide, acting as an endogenous ligand of the NOP receptor. The NOP receptor has wide expression in the central nervous system and its activation induces inhibitory effects, causing reduction of neurotransmitters release and/or inhibition of neuronal firing, depending on the site (pre or post-synaptic) in which it is expressed. In vivo studies have showed the involvement of the N/OFQ-NOP receptor system in the modulation of emotional states. This study aimed to evaluate the effects of the NOP agonist, Ro65-6570, on the mouse behavioral changes after an uncontrollable stressful situation due to unpredictable electric footshocks. To achieve this aim, the learned helplessness model (LH) was used as a stressor to induce a helpless behavior. Helpless phenotype consists of a deficit in the escape behavior of the electrified compartment. Not all animals exposed to the LH developed the helpless phenotype, and then two distinct groups were observed: helpless and non-helpless mice. After the LH, tests were performed aimed to identify the behavioral changes induced by stress, such as elevated plus maze (EPM), forced swimming and open field. LH exposure induced anxiogenic-like effects in helpless mice. In fact, when compared to non-helpless and naive controls, helpless mice displayed decreased number of entries and time spent in the open arms of the EPM. After then, the effects of diazepam (1 mg/kg, via ip) and the NOP agonist, Ro65-6570 (1 mg/kg, via ip) were assessed in the anxiogenic-like behavior of helpless mice, as well as in spontaneous locomotion. Diazepam was able to reverse the anxiogenic-related behaviors of helpless mice in the EPM, without affecting locomotion. Similarly, the administration of Ro65-6570 induced anxiolytic effects only in helpless mice, without changes in the locomotor activity. In conclusion, this study supports to the N/OFQ-NOP receptor system as an innovative therapeutic target for the treatment of psychiatric disorders related to stress.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/24443 |
| Date | 27 April 2017 |
| Creators | Azevedo Neto, Joaquim Gon?alves de |
| Contributors | 97013390968, Rachetti, Vanessa de Paula Soares, 28762725807, Salvadori, Mirian Graciela da Silva Stiebbe, 94533261000, Gavioli, Elaine Cristina |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM PSICOBIOLOGIA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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