Banca de DEFESA: MARGARETH DE BRITO NOGUEIRA LIMA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARGARETH DE BRITO NOGUEIRA LIMA
DATE: 31/03/2022
TIME: 09:00
LOCAL: meet.google.com/rcz-pzpc-qnp
TITLE:

On the anxiolytic effects of 5-MeO-DMT in the mouse brain and behavior

KEY WORDS:

5-MeO-DMT, serotonergic psychedelics, anxiety, plasticity, neuronal activity, basolateral amygdala, anterior cingulate cortex, ventral CA1, ventral dentate gyrus

PAGES: 133
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

Anxiety is a worldwide prevalent circuitopathy, in other words, a circuit disorder that substantially affects people's quality of life. To treat it properly, it is necessary to reverse the processes that lead to the malfunctioning of neuronal circuits mainly implicated in anxiety behavior. There is still no completely effective treatment for such a disorder. Several studies have presented promising and safe results with serotonergic psychedelics, evidencing the therapeutic potential of these compounds. However, their mechanisms of action have not yet been fully elucidated. Many clinical studies have managed to durably mitigate the symptoms of depression and anxiety with just a single dose, which makes these compounds very interesting alternatives to the classical treatments available in psychiatry. These lasting effects can be explained by a possible induction of neuroplasticity, neuroprotection, and modulation of inflammation-related agents. Some studies have shown an increase in neuritogenesis, synaptogenesis, and neurogenesis from treatment with psychedelic compounds. In this study, we sought to identify how the serotonergic psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) durably affects neuronal activity and the expression of plasticity-related genes in brain structures classically related to anxiety, such as the basolateral amygdala, the ventral hippocampus, and the anterior cingulate cortex of adult mice one hour, five hours, and five days after treatment. Assessing the electrophysiological properties of mice after 5 days of 5-MeO-DMT treatment, we found differences in passive membrane properties, as well as changes in amplitude and frequency of neuronal firing. Evaluating gene expression one hour after treatment, we showed increased expression of ARC and ZIF268 immediate early genes in the anterior cingulate cortex and basolateral amygdala. After 5 hours of treatment, the NR2A gene was significantly decreased in ventral CA1. Finally, 5 days after the treatment with 5-MeO-DMT we found a significant increase of the TRIP8b gene in ventral CA1. We then intended to see if 5-MeO-DMT produces changes in the behavior of mice after 24hours and 5 days of treatment, with and without stress conditions. We also assessed mice basal corticosterone serum levels under and after acute restraint stress. We found that 5-MeO-DMT treated mice presented significantly less basal corticosterone levels after 5 days. They also presented less anxious behavior. These molecular, cellular, and behavioral findings suggest that 5-MeO-DMT produces immediate and long-lasting effects in mice, although further studies are necessary to consider the therapeutic possibility and to unravel which signaling pathways underlie the 5-MeO-DMT role on synaptic plasticity. 

BANKING MEMBERS:
Externo à Instituição - RAFAEL GUIMARÃES DOS SANTOS - USP
Externo ao Programa - 2069422 - DIEGO ANDRES LAPLAGNE
Externa ao Programa - 1645202 - ELAINE CRISTINA GAVIOLI
Interna - 1976236 - EMELIE KATARINA SVAHN LEAO
Externo à Instituição - OLAVO BOHRER AMARAL - UFRJ
Presidente - 1824636 - RICHARDSON NAVES LEAO