Banca de QUALIFICAÇÃO: MARIO FERNANDO DA COSTA PINTO NETO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIO FERNANDO DA COSTA PINTO NETO
DATE: 19/10/2026
TIME: 08:30
LOCAL: Videoconferência
TITLE:

Effects of N,N-dimethyltryptamine (DMT) and its relationship with the indoleamine 2,3-dioxygenase 1 (IDO-1) pathway: a behavioral, molecular, and genitourinary tract contractility assessment.

KEY WORDS:

Kynurenines; indoleamine 2,3-dioxygenase 1; depression; N,N-dimethyltryptamine.

PAGES: 87
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Introduction: Mental disorders represent a significant cause of disability worldwide, with depression and its emotional, cognitive, and somatic repercussions being particularly noteworthy. Beyond mood alterations, this condition can cause dysfunctions in the gastrointestinal and genitourinary systems, potentially related to modifications in monoaminergic neurotransmission, the hypothalamic-pituitary-adrenal axis, and immunoinflammatory processes. In this context, serotonergic signaling and the kynurenine pathway have been investigated as possible components in the pathophysiology of depression and its somatic manifestations. As an alternative to conventional antidepressants – frequently associated with adverse effects and a long latency to the onset of therapeutic effect – N,N-dimethyltryptamine (DMT), a tryptamine with serotonergic activity, has been investigated due to its potential to produce rapid antidepressant responses. Objectives: To test the hypothesis that N,N-dimethyltryptamine (DMT) modifies behaviors associated with depression generated by exposure to chronic mild unpredictable stress (CUMS), by altering the kynurenine/IDO-1 pathway. Methods: Wistar rats will be used, maintained under controlled conditions of temperature, lighting, and access to water and food. The animals will be subjected to a 28-day protocol of chronic mild unpredictable stress (CUMS). After this period, independent groups will receive saline solution, DMT at doses of 10 or 20 mg/kg, or ketamine at a dose of 10 mg/kg. Anhedonia will be assessed using the cookie test on days 0, 28, and 35. Twenty-four hours after treatment, a battery of behavioral tests will begin, consisting of the elevated plus maze, open field, forced swim, and footshock stress, organized in ascending order of aversive potential. On day 35, the animals will be euthanized for collection of biological material for biochemical, molecular, and tissue analyses, including evaluation of IDO-1 expression and activity and the kynurenine pathway. To date, isolated organ baths have been performed to determine the effects of DMT on the contractile activity and pharmacological reactivity of the gastric fundus and bladder of males. Expected results: The CUMS protocol is expected to induce changes in behavioral tests consistent with a depressive and anxious-like phenotype, including anhedonia, accompanied by biochemical and molecular changes related to the kynurenine pathway. Treatment with DMT, particularly at doses of 10 and 20 mg/kg, is expected to attenuate these behavioral changes, showing effects similar to or comparable to those observed after ketamine administration. At the molecular level, DMT is expected to reduce the expression and/or activity of IDO-1 and, consequently, the metabolism of the kynurenine pathway, contributing to the understanding of the mechanisms associated with its possible antidepressant effects. Additionally, it is expected to identify possible differences between males and females in the response to the drug. In experiments with isolated organs, it was observed that DMT did not significantly alter the contractility of the bladder and gastric fundus in males. However, it is expected to characterize the effects of DMT on the contractile activity and pharmacological reactivity of the colon, jejunum, gastric fundus, and bladder of females, as well as to verify possible sex-related differences. Conclusion: To date, DMT has not shown a significant effect on the contractility of the bladder and gastric fundus of rats. The overall conclusion of the study will depend on the integration of these findings with the behavioral, biochemical, and molecular results, contributing to the characterization of the effects of DMT and its possible mechanisms of action in the context of chronic stress.

COMMITTEE MEMBERS:
Presidente - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Externa ao Programa - 1645202 - ELAINE CRISTINA GAVIOLI - UFRNExterna à Instituição - MIRIAN GRACIELA DA SILVA STIEBBE SALVADORI - UFPB