Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats

Detalhes bibliográficos
Autor(a) principal: Sant'Ana, Ana Beatriz
Data de Publicação: 2019
Outros Autores: Vilela-Costa, Heloisa Helena, Vicente, Maria Adrielle, Hernandes, Paloma Molina, de Andrade, Telma Gonçalves Carneiro Spera [UNESP], Zangrossi, Hélio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.neuropharm.2019.01.026
http://hdl.handle.net/11449/187314
Resumo: The role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine.
id UNSP_3d7aadec7c592bb36bd5d9de174ef7a7
oai_identifier_str oai:repositorio.unesp.br:11449/187314
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats5-HT2C receptorAnxietyDorsal hippocampusElevated T-mazeImipramineSerotoninThe role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo (USP)Department of Biological Science São Paulo State University (UNESP)Department of Biological Science São Paulo State University (UNESP)FAPESP: 2012/20016-6FAPESP: 2017/18437-7Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Sant'Ana, Ana BeatrizVilela-Costa, Heloisa HelenaVicente, Maria AdrielleHernandes, Paloma Molinade Andrade, Telma Gonçalves Carneiro Spera [UNESP]Zangrossi, Hélio2019-10-06T15:32:22Z2019-10-06T15:32:22Z2019-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article311-319http://dx.doi.org/10.1016/j.neuropharm.2019.01.026Neuropharmacology, v. 148, p. 311-319.1873-70640028-3908http://hdl.handle.net/11449/18731410.1016/j.neuropharm.2019.01.0262-s2.0-85060960618Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeuropharmacologyinfo:eu-repo/semantics/openAccess2021-10-23T15:55:12Zoai:repositorio.unesp.br:11449/187314Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:22:00.970538Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
title Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
spellingShingle Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
Sant'Ana, Ana Beatriz
5-HT2C receptor
Anxiety
Dorsal hippocampus
Elevated T-maze
Imipramine
Serotonin
title_short Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
title_full Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
title_fullStr Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
title_full_unstemmed Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
title_sort Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats
author Sant'Ana, Ana Beatriz
author_facet Sant'Ana, Ana Beatriz
Vilela-Costa, Heloisa Helena
Vicente, Maria Adrielle
Hernandes, Paloma Molina
de Andrade, Telma Gonçalves Carneiro Spera [UNESP]
Zangrossi, Hélio
author_role author
author2 Vilela-Costa, Heloisa Helena
Vicente, Maria Adrielle
Hernandes, Paloma Molina
de Andrade, Telma Gonçalves Carneiro Spera [UNESP]
Zangrossi, Hélio
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Sant'Ana, Ana Beatriz
Vilela-Costa, Heloisa Helena
Vicente, Maria Adrielle
Hernandes, Paloma Molina
de Andrade, Telma Gonçalves Carneiro Spera [UNESP]
Zangrossi, Hélio
dc.subject.por.fl_str_mv 5-HT2C receptor
Anxiety
Dorsal hippocampus
Elevated T-maze
Imipramine
Serotonin
topic 5-HT2C receptor
Anxiety
Dorsal hippocampus
Elevated T-maze
Imipramine
Serotonin
description The role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-06T15:32:22Z
2019-10-06T15:32:22Z
2019-04-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.neuropharm.2019.01.026
Neuropharmacology, v. 148, p. 311-319.
1873-7064
0028-3908
http://hdl.handle.net/11449/187314
10.1016/j.neuropharm.2019.01.026
2-s2.0-85060960618
url http://dx.doi.org/10.1016/j.neuropharm.2019.01.026
http://hdl.handle.net/11449/187314
identifier_str_mv Neuropharmacology, v. 148, p. 311-319.
1873-7064
0028-3908
10.1016/j.neuropharm.2019.01.026
2-s2.0-85060960618
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Neuropharmacology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 311-319
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128637953638400