Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.

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Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1μM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25μM, (PhSe)2 did not elicit effects on fish behavior. At 0.5μM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1μM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25μM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25μM (PhSe)2 showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty.

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Ao meu orientador Rodrigo, que teve uma paciência do tamanho do universo, que me acolheu e orientou com tanto zelo. Aos membros da banca, Prof. Márcia Veirano e Prof. Roberto Assis pelas incríveis considerações que tornaram o curso do meu trabalho ainda mais grandioso.Ao professor Marcelo Buzato, por sempre ter apoiado minhas maluquices tecnológicas, ter me guiado brilhantemente durante suas aulas incríveis e por suas considerações imprescindíveis na qualificação.Às minhas amigas Bruna e Aline, por serem minhas irmãs de coração, que sempre me seguraram quando eu estava prestes a cair. Pela cumplicidade.Aos meus amigos de luta, de RU e feirinha: Daniel, Tiêgo, Izadora, Ludmilla e Gabriel. Especialmente ao Daniel, que sempre esteve do meu lado e que se tornou um amigo para vida. Ao Tiêgo, pela força e playlists incríveis.Às minhas amigas Marina Sansão e Juliana Goulart, por todo apoio, amor, vinhos, choros e risadas.Ao meu amigo Rauster, que sempre esteve ao meu lado e por ser o único que sobrou, desde os primórdios do fim do mundo (o que foi em 2012) e da faculdade.Aos amigos e membros do grupo de pesquisa Mídites, em especial Rodrigo, Marco, Izadora, Maristella e Terezinha, que sempre estiveram ao meu lado com suas contribuições.