Banca de QUALIFICAÇÃO: FERNANDA MARIA ARAUJO DE SOUZA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : FERNANDA MARIA ARAUJO DE SOUZA
DATE: 09/12/2021
TIME: 09:00
LOCAL: Instituto de Ciências Biológicas e da Saúde, ICBS
TITLE:

VALIDATION OF A NEW ANIMAL MODEL IN THE STUDY OF ANXIETY AND DEPRESSION IN MICE INDUCED BY A LOW 

DOSE OF PILOCARPINE

KEY WORDS:

Animal model. Mental disorders. Pharmacological validity. Mice. Pilocarpine.

PAGES: 61
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUBÁREA: Neuropsicofarmacologia
SUMMARY:

Animal models for the study of anxiety and depression disorders are important tools for understanding the pathophysiology and developing new pharmacological therapies. Recently, studies have shown that subconvulsant doses of pilocarpine (PILO; nonselective muscarinic receptor agonist) produce short- and long-term anxiogenic-like behavior in Wistar rats. Our research group extended these data by demonstrating that Swiss mice (of both sexes) showed anxiogenic and depressive-like behavior after treatment with a low dose of PILO, with females being more susceptible to long-term effects. This research aimed to evaluate the pharmacological validity of this new animal model for anxiety and depression induced after administration of a low dose of PILO in mice. Futhermore, we also aimed to investigate serum levels of corticosterone and hippocampal neurogeneration. For pharmacological validity, Swiss mice received a PILO-injection (75 mg/Kg, i.p.) and 24 hours or for 30 consecutive days after were treated with diazepam (1.5 mg / Kg, i.p.) or fluoxetine (10 mg/Kg, i.p.). The short- (24h) and long-term (30d) effects of the treatments on behaviors related to fear, anxiety and depression were observed in the elevated plus-maze (EPM) and forced swim (FS) tests, respectively. The spontaneous locomotor activity of the animals was evaluated in the open field (OF). After the tests, blood and brains were collected from the animals to analyze the serum levels of corticosterone and hippocampal neurodegeneration (by Fluoro-Jade C; FJ-C). As a result, we observed that treatment with diazepam blocked both short- and long-term anxiogenic-like behavior (e.g., increased time and number of open arms entries in the EPM) induced by PILO, but not depressive-like behavior in the NF. Treatment with fluoxetine was able to block the anxiogenic-(e.g. increased time and number of open arms entries in the EPM) and depressive-like (e.g. decreased immobility time in the NF) behavior induced by PILO only in the long-term. Animals treated with PILO and later with diazepam or fluoxetine did not show changes in spontaneous locomotion in the OF. Treatment with PILO increased serum corticosterone levels in the short-, but not in the long-term. After 24h or 30d, animals treated with PILO did not show hippocampal neurodegeneration (FJ-C-). These results showed that the anxiogenic- and depressive-like behaviors induced by PILO can be blocked with acute or chronic treatment with standard anxiolytic and antidepressant, in a similar way to that found in the clinic, demonstrating the pharmacological validity of this new animal model.

BANKING MEMBERS:
Externo à Instituição - AXEL HELMUT RULF COFRE - CESMAC
Interno - 2579081 - DANIEL LEITE GOES GITAI
Externo à Instituição - FILIPE SILVEIRA DUARTE - UFPE
Presidente - 2033893 - MARCELO DUZZIONI