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No. of bitstreams: 1 FlaviaSantosDaSilva_DISSERT.pdf: 2709204 bytes, checksum: 558d5dd8275d80014abfc2fe06dec020 (MD5) Previous issue date: 2017-07-05 / O Transtorno de Depress?o Maior (TDM) ? um dist?rbio de humor de alcance global, atingindo aproximadamente 350 milh?es de pessoas em todo o mundo, capaz de induzir preju?zos psicol?gicos, sociais e fisiol?gicos, que podem em alguns casos, levar ? morte por suic?dio. 14 % dos jovens entre 15-18 anos apresentam TDM, o que desperta aten??o e preocupa??o, j? que esta fase constitui um per?odo ontogen?tico de grandes modifica??es cerebrais que perduram por toda a vida. Atualmente, o tratamento antidepressivo mais empregado em todas as faixas et?rias ? o farmacol?gico. Embora as classes mais modernas de antidepressivos sejam mais espec?ficas em sua a??o, ainda apresentam efeitos colaterais consider?veis, demoram at? duas semanas para iniciar os efeitos terap?uticos desejados e induzem baixa taxa de remiss?o. Sendo assim, h? a necessidade de se buscar novos tratamentos farmacol?gicos para essa doen?a, nesse cen?rio algumas subst?ncias psicod?licas serotonin?rgicas v?m sendo testadas. O ch? de ayahuasca, tradicional da Amaz?nia, tem particularmente chamado a aten??o por seus efeitos positivos na sa?de, tanto na popula??o geral de usu?rios quanto em pacientes com transtornos de humor e viciados em drogas de abuso. Para testar a a??o antidepressiva aguda da ayahuasca utilizamos o Callithrix jacchus, um primata n?o-humano que j? vem sendo considerado um importante modelo em estudos biom?dicos, inclusive de desordens mentais, pois apresenta maior proximidade filogen?tica aos humanos, possui um etograma bem definido, t?cnicas n?o invasivas para medi??o de cortisol em fezes, boa adapta??o em cativeiro e alta taxa de fecundidade. Entretanto, inicialmente foi necess?rio proceder com a valida??o da esp?cie como modelo translacional de depress?o juvenil. Para isso foram utilizados dois procedimentos experimentais de isolamento social cr?nico, em machos e f?meas de C. jacchus juvenis, que induziu um estado fisiol?gico e comportamental caracter?stico de depress?o em primatas n?o-humanos, o qual foi em grande parte revertido pelo tratamento com um antidepressivo cl?ssico, a nortriptilina, inoculada por 7 dias, e n?o por um ve?culo (salina; 7 dias). Esse estudo e seus respectivos resultados est?o descritos no artigo I intitulado ?Common marmosets: A potential translational animal model of juvenile depression?, publicado no peri?dico Frontiers in Psychiatry. Em seguida, testamos o potencial antidepressivo agudo do ch? de ayahuasca, no modelo translacional previamente validad. Assim, originou-se o artigo II intitulado ?Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression?, submetido no peri?dico Frontiers in Pharmacology. Observamos que uma dose ?nica de ayahuasca, e n?o do ve?culo (salina), induziu melhoras em parte dos sintomas depressivos por at? 14 dias e reestabeleceu, de forma r?pida, 24 horas ap?s a ingest?o, os n?veis de cortisol aos valores basais, encontrados quando os animais habitavam a gaiola familiar. Sendo assim, observa-se que o ch? de ayahuasca apresentou resultados antidepressivos mais interessantes que a nortriptilina, uma vez que a ayahuasca induziu a revers?o dos sintomas mais rapidamente, de maneira mais ajustada e duradoura que a nortriptilina. Ambos os estudos aqui apresentados s?o de grande relev?ncia para ?rea, uma vez que de maneira in?dita um modelo animal translacional de depress?o com primatas n?o-humanos atendeu a todos os crit?rios de valida??o, tanto os tradicionais, como; o etiol?gico, de face, funcional e preditivo, quanto os crit?rios mais recentes: o inter-relacional, evolutivo e populacional, possibilitando assim a sua utiliza??o em ?reas complementares de investiga??es. Adicionalmente, foi apresentado n?o apenas a??es antidepressivas aguda do ch? da ayahuasca, mais tamb?m a??es mais eficazes quando comparado com um antidepressivo cl?ssico, nortriptilina, corroborando assim no processo de valida??o desta subst?ncia como antidepressivo, estimulando novas investiga??es farmacologicas, inclusive em adolescentes, que possibilitem a consolida??o do ch? como antidepressivo, uma vez que ela n?o tem demonstrado tolerancia ? doses, nem efeitos colaterias de longo prazo em usu?rios recreacionais. / The Major Depression Disorder (MDD) is a mood disorder of global reach, reaching approximately 350 million people, capable to induce psychological, social and physiological impair, which in some cases can lead to death by suicide. 14% of young people aged 15-18 have MDD that provoke attention and apprehension, since this phase consist an ontogenetic period of major brain modifications that last for the all lives. Currently, the most commonly used antidepressant treatment in all age groups is the pharmacological treatment. Although the newer classes of antidepressants are more specific in their action, they still have considerable side effects, take up to two weeks to initiate the desired therapeutic effects and induce low rate of remission. Thereby, there is a necessity to seek new pharmacological treatments for this disease. In this scenario, have been tested some psychedelic serotonergic substances. The ayahuasca tea, a traditional Amazonian tea, has particularly drawn attention by its positive effects on health, both in the general population of users and in patients with mood disorders and drug addicts. To test the acute antidepressant action of ayahuasca was used Callithrix jacchus, a non-human primate that has already been considered an important model in biomedical studies, including mental disorders, because it?s more phylogenetic proximity to humans, has a well-defined etogram, invasive methods for measuring cortisol in feces, good adaptation in captivity and high fecundity rate. However, it was initially necessary to validate the species as a translational model of juvenile depression. For this purpose, two experimental procedures of chronic social isolation were used in males and females of C. jacchus juveniles, which induced a physiological and behavioral state characteristic of depression in nonhuman primates, which was largely reversed by treatment with an antidepressant nortriptyline, inoculated for 7 days, rather than vehicle (vehicle, 7 days). This study and its results are described in article I entitled " Common marmosets: A potential translational animal model of juvenile depression", published in the Journal Frontiers in Psychiatry. We then tested the acute antidepressant potential of ayahuasca tea in the previously validated translational model. Thus, was originated the article II entitled "Acute antidepressant effect of Ayahuasca in juvenile non-human primate model of depression", which was submitted in the journal Frontiers in Pharmacology . We observed that a single dose of ayahuasca, not vehicle (saline), induced improvements in part of depressive-like symptoms for up to 14 days and quickly restored 24 hours after ingestion to cortisol levels at baseline, when the animals inhabited the family cage. Thus, it is observed that ayahuasca tea presented more interesting antidepressant results than nortriptyline, since ayahuasca induced the reversal of symptoms more quickly, in a more adjusted and lasting way that nortriptyline. Both studies presented here are of great relevance to the area, since in an unpublished way a translational animal model of depression with nonhuman primates met all validation criteria, both traditional, the etiological, face, functional and predictive, as well as the most recent criteria: the inter-relational, evolutionary and population, thus enabling its use in complementary areas of investigation. In addition, not only acute antidepressant actions of ayahuasca tea were presented, but also more affective actions when compared with a classic antidepressant, nortriptyline, thus corroborating in the validation process of this drug as antidepressant, stimulating new pharmacological investigations, including in adolescents, that make possible the consolidation of tea as an antidepressant, since it has not shown tolerance to doses, nor long-term side effects in recreational users.