Investigation of the role of 5-HT1A receptors located in the lateral wings of the dorsal raphe nucleus on the panicolytic effect promoted by fluoxetine treatment

• Grant number: 17/18437-7
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): January 01, 2018
• Effective date (End): February 28, 2021
• 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

Abstract

The pharmacological treatment of panic disorder made my using antidepressant drugs that act through the selective serotonin reuptake inhibition (SSRI) such as fluoxetine. Although they have proved efficacy, the therapeutic effects are observed only after prolonged and continuous administration. One of the most accepted theories that try to explain the neurobiological mechanism triggered by the SSRI during the time, propose that the antidepressant effect is observed only after the desensitization of the inhibitory 5-HT1A autoreceptor located in the dorsal raphe nucleus (DRN). A wealth of evidences subsequents to this proposal indicate that the DRN is a heterogeneous structure, composed by sub-regions of neurons, serotonergic and non-serotonergic, that express 5-HT1A receptors in a different way, anatomically and functionally. Within the framework, the proposal of the present work is extend the investigations about the role of 5-HT1A receptors located in the lateral wings of the DRN (a region involved in panic-related responses) in the panicolytic effect of fluoxetine. Initially, this project aims to assess the generality of the effect of chronic treatment with fluoxetine in the recruitment serotonergic and non-serotonergic neurons located in the DRN, by using the hypoxia exposure, an experimental model of panic. In the second stage of the study, electrophysiological analyzes will be performed by using whole cell patch-clamp in order to verify the response of 5-HT1A expressed in non-serotonergic neurons located on the lateral wings of the DRN after acute or chronic treatment with fluoxetine; and, the phenotype of these neurons will be investigated by using the single-cell RT-PCR technique.

Scientific publications

(7)

(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)

HERNANDES, PALOMA MOLINA; BATISTELA, MATHEUS FITIPALDI; VILELA-COSTA, HELOISA HELENA; SANT `ANA, ANA BEATRIZ; KUMPEL, VINICIUS DIAS; TIRAPELLE, MARIANE CARIATI; BOM, ARIELA DE OLIVEIRA PEDRO; DE ANDRADE, TELMA GONCALVES CARNEIRO SPERA; ZANGROSSI JR, HELIO. Role of 5-HT1A receptors in the ventral hippocampus in the regulation of anxiety- and panic-related defensive behaviors in rats. Behavioural Brain Research, v. 408, JUN 25 2021. (16/16015-5, 17/18437-7)

SANT'ANA, ANA BEATRIZ; VILELA-COSTA, HELOISA HELENA; VICENTE, MARIA ADRIELLE; HERNANDES, PALOMA MOLINA; CARNEIRO SPERA DE ANDRADE, TELMA GONCALVES; ZANGROSSI, JR., HELLO. Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats. Neuropharmacology, v. 148, p. 311-319, APR 2019. (12/20016-6, 17/18437-7)

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, SEP 2019. (13/05903-9, 17/18437-7)

BATISTELA, MATHEUS F.; VILELA-COSTA, HELOISA H.; FRIAS, ALANA T.; HERNANDES, PALOMA M.; LOVICK, THELMA A.; ZANGROSSI, JR., HELIO. Enhanced responsiveness to hypoxic panicogenic challenge in female rats in late diestrus is suppressed by short-term, low-dose fluoxetine: Involvement of the dorsal raphe nucleus and the dorsal periaqueductal gray. JOURNAL OF PSYCHOPHARMACOLOGY, v. 35, n. 12, p. 1523-1535, DEC 2021. (17/18437-7, 19/05240-6)

BATISTELA, MATHEUS F.; VILELA-COSTA, HELOISA H.; FRIAS, ALANA T.; HERNANDES, PALOMA M.; LOVICK, THELMA A.; ZANGROSSI JR, HELIO. Enhanced responsiveness to hypoxic panicogenic challenge in female rats in late diestrus is suppressed by short-term, low-dose fluoxetine: Involvement of the dorsal raphe nucleus and the dorsal periaqueductal gray. JOURNAL OF PSYCHOPHARMACOLOGY, v. 35, n. 12, DEC 2021. (17/18437-7, 19/05240-6)

DE OLIVEIRA SERGIO, THATIANE; FRIAS, ALANA TERCINO; VILELA-COSTA, HELOISA HELENA; DE OLIVEIRA, DANIELLE C. G.; ZUARDI, ANTONIO W.; ZANGROSSI JR, HELIO. Serotonin mediates the panicolytic-like effect of oxytocin in the dorsal periaqueductal gray. JOURNAL OF PSYCHOPHARMACOLOGY, v. 34, n. 4, FEB 2020. (17/18437-7)

LOVICK, THELMA A.; ZANGROSSI JR, HELIO. Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety. FRONTIERS IN PSYCHIATRY, v. 12, AUG 31 2021. (17/18437-7, 19/05240-6)