Estudo do efeito agudo dos compostos ativos do chá de Ayahuasca (Banisteriopsis Caapi e Psychotria Viridi), em saguis (Callithrix jacchus) como modelo animal de depressão juvenil

Abstract

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.