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Effect of administration of fluoxetine and imipramine on serotonergic neurotransmission in different subregions of the dorsal raphe nucleus and dorsal periaqueductal gray of rats exposed to model elevated T maze

Grant number: 13/05903-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Hélio Zangrossi Júnior
Grantee:Heloísa Helena Vilela Costa
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders, AP.TEM
Associated scholarship(s):15/11782-5 - Effects of fluoxetine on 5-HT1A receptors located in different dorsal raphe subnuclei: an optogenetic and eletrophysiological approach, BE.EP.DR


The mechanisms of anxiolytic and panicolytic actions of antidepressant drugs (ADs) have been the subject of great interest. Our research group has demonstrated that in animals treated chronically with ADs occurs facilitation of neurotransmission mediated by serotonergic 5-HT1A and 5-HT2A receptors in the periaqueductal gray (PAG). This change is associated with the inhibitory effect of ADs on the expression of escape behavior, considered a panicolytic-like response. However, some aspects of the involvement of 5-HT2A receptors and other subtypes of serotonin receptors present in PAG, such as 5-HT2C, in mediating the effects of ADs in experimental anxiety are still poorly understood. In this study, we will investigate if the anti-scape effect caused by chronic administration of fluoxetine and imipramine in the elevated T-maze (LTE) is blocked by administration of receptor 5-HT2A antagonist in the SCPD, as occur with the microinjection of receptor 5 -HT1A antagonists. We will also verify if the blockade of 5-HT2C receptors in the SCPD interferes with the anxiogenic effect caused by acute administration of ADs and if the reactivity of these receptors is changed after prolonged treatment with the same drugs. In the second stage of the study, we will investigate the profile of neuronal activation of different dorsal raphe nucleus subregions (DRN) (evaluating the expression of Fos protein, with double-labeled for the enzyme tryptophan hydroxylase), after acute and chronic administration of imipramine and fluoxetine. The DRN is the main source of serotonergic innervation to the PAG. Although many studies show the importance of alterations in the functioning of serotonergic neurons of the DRN to the ADs effects, it is still unknown whether these alterations may be heterogeneous between different sub-regions of this nucleus.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VILELA-COSTA, HELOISA HELENA; SPIACCI JR, AILTON; BISSOLLI, ISABELLA GALANTE; ZANGROSSI JR, HELIO. A Shift in the Activation of Serotonergic and Non-serotonergic Neurons in the Dorsal Raphe Lateral Wings Subnucleus Underlies the Panicolytic-Like Effect of Fluoxetine in Rats. Molecular Neurobiology, v. 56, n. 9, p. 6487-6500, . (13/05903-9, 17/18437-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
COSTA, Heloísa Helena Vilela. Involvement of different subregions of the dorsal raphe nucleus in the anti-panic action mechanism of antidepressant drugs. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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