Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice

Detalhes bibliográficos
Autor(a) principal: Falconi-Sobrinho, Luiz Luciano
Data de Publicação: 2023
Outros Autores: dos Anjos-Garcia, Tayllon, Hernandes, Paloma Molina [UNESP], Rodrigues, Bruno Mangili de Paula, Almada, Rafael Carvalho [UNESP], Coimbra, Norberto Cysne
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s00213-023-06309-7
http://hdl.handle.net/11449/248215
Resumo: Rationale: Previous studies suggested that the dorsal column of the periaqueductal grey matter (dPAG) can be a target of neural pathways from hypothalamic nuclei involved in triggering fear-related defensive responses. In turn, evidence is provided suggesting that microinjection of the nitric oxide (NO) donor SIN-1 into the anterior hypothalamus (AH) of mice evokes panic-like behaviours and fear-induced antinociception. However, it is unknown whether the dPAG of mice mediates these latter defensive responses organised by AH neurons. Objectives: This study was designed to examine the role of dPAG in mediating SIN-1-evoked fear-induced defensive behavioural and antinociceptive responses organised in the AH of mice. Methods: First, neural tract tracing was performed to characterise the AH-dPAG pathways. Then, using neuropharmacological approaches, we evaluated the effects of dPAG pretreatment with either the non-selective synaptic blocker cobalt chloride (CoCl2; 1 mM/0.1 μL) or the competitive N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (0.1 nmol/0.1 μL) on defensive behaviours and antinociception induced by microinjections of SIN-1 in the AH of male C57BL/6 mice. Results: AlexaFluor488-conjugated dextran-labelled axonal fibres from AH neurons were identified in both dorsomedial and dorsolateral PAG columns. Furthermore, we showed that pre-treatment of the dPAG with either CoCl2 or LY235959 inhibited freezing and impaired oriented escape and antinociception induced by infusions of SIN-1 into the AH. Conclusions: These findings suggest that the panic-like freezing and oriented escape defensive behaviours, and fear-induced antinociception elicited by intra-AH microinjections of SIN-1 depend on the activation of dPAG NMDA receptors.
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spelling Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male miceAnterior hypothalamusDefensive behaviourFear-induced analgesiaNitric oxideNMDA receptorsPeriaqueductal grey matterStressRationale: Previous studies suggested that the dorsal column of the periaqueductal grey matter (dPAG) can be a target of neural pathways from hypothalamic nuclei involved in triggering fear-related defensive responses. In turn, evidence is provided suggesting that microinjection of the nitric oxide (NO) donor SIN-1 into the anterior hypothalamus (AH) of mice evokes panic-like behaviours and fear-induced antinociception. However, it is unknown whether the dPAG of mice mediates these latter defensive responses organised by AH neurons. Objectives: This study was designed to examine the role of dPAG in mediating SIN-1-evoked fear-induced defensive behavioural and antinociceptive responses organised in the AH of mice. Methods: First, neural tract tracing was performed to characterise the AH-dPAG pathways. Then, using neuropharmacological approaches, we evaluated the effects of dPAG pretreatment with either the non-selective synaptic blocker cobalt chloride (CoCl2; 1 mM/0.1 μL) or the competitive N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (0.1 nmol/0.1 μL) on defensive behaviours and antinociception induced by microinjections of SIN-1 in the AH of male C57BL/6 mice. Results: AlexaFluor488-conjugated dextran-labelled axonal fibres from AH neurons were identified in both dorsomedial and dorsolateral PAG columns. Furthermore, we showed that pre-treatment of the dPAG with either CoCl2 or LY235959 inhibited freezing and impaired oriented escape and antinociception induced by infusions of SIN-1 into the AH. Conclusions: These findings suggest that the panic-like freezing and oriented escape defensive behaviours, and fear-induced antinociception elicited by intra-AH microinjections of SIN-1 depend on the activation of dPAG NMDA receptors.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratory of Neuroanatomy and Neuropsychobiology Department of Pharmacology Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão PretoNAP-USP-Neurobiology of Emotions (NuPNE) Research Centre Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão PretoBehavioural Neurosciences Institute (INeC), Avenida do Café, 2450, Ribeirão PretoBiomedical Sciences Institute of the Federal University of Alfenas (UNIFAL), Minas GeraisDepartment of Biological Sciences School of Science Humanities and Languages São Paulo State University (UNESP), AssisDepartment of Biological Sciences School of Science Humanities and Languages São Paulo State University (UNESP), AssisFAPESP: 2007/01174-1FAPESP: 2012/03798-0FAPESP: 2017/11855-8FAPESP: 2020/15050-7Universidade de São Paulo (USP)Behavioural Neurosciences Institute (INeC)Biomedical Sciences Institute of the Federal University of Alfenas (UNIFAL)Universidade Estadual Paulista (UNESP)Falconi-Sobrinho, Luiz Lucianodos Anjos-Garcia, TayllonHernandes, Paloma Molina [UNESP]Rodrigues, Bruno Mangili de PaulaAlmada, Rafael Carvalho [UNESP]Coimbra, Norberto Cysne2023-07-29T13:37:43Z2023-07-29T13:37:43Z2023-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article319-335http://dx.doi.org/10.1007/s00213-023-06309-7Psychopharmacology, v. 240, n. 2, p. 319-335, 2023.1432-20720033-3158http://hdl.handle.net/11449/24821510.1007/s00213-023-06309-72-s2.0-85146383559Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPsychopharmacologyinfo:eu-repo/semantics/openAccess2024-06-13T17:38:53Zoai:repositorio.unesp.br:11449/248215Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:55:36.043176Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
title Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
spellingShingle Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
Falconi-Sobrinho, Luiz Luciano
Anterior hypothalamus
Defensive behaviour
Fear-induced analgesia
Nitric oxide
NMDA receptors
Periaqueductal grey matter
Stress
title_short Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
title_full Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
title_fullStr Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
title_full_unstemmed Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
title_sort Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic‑like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice
author Falconi-Sobrinho, Luiz Luciano
author_facet Falconi-Sobrinho, Luiz Luciano
dos Anjos-Garcia, Tayllon
Hernandes, Paloma Molina [UNESP]
Rodrigues, Bruno Mangili de Paula
Almada, Rafael Carvalho [UNESP]
Coimbra, Norberto Cysne
author_role author
author2 dos Anjos-Garcia, Tayllon
Hernandes, Paloma Molina [UNESP]
Rodrigues, Bruno Mangili de Paula
Almada, Rafael Carvalho [UNESP]
Coimbra, Norberto Cysne
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Behavioural Neurosciences Institute (INeC)
Biomedical Sciences Institute of the Federal University of Alfenas (UNIFAL)
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Falconi-Sobrinho, Luiz Luciano
dos Anjos-Garcia, Tayllon
Hernandes, Paloma Molina [UNESP]
Rodrigues, Bruno Mangili de Paula
Almada, Rafael Carvalho [UNESP]
Coimbra, Norberto Cysne
dc.subject.por.fl_str_mv Anterior hypothalamus
Defensive behaviour
Fear-induced analgesia
Nitric oxide
NMDA receptors
Periaqueductal grey matter
Stress
topic Anterior hypothalamus
Defensive behaviour
Fear-induced analgesia
Nitric oxide
NMDA receptors
Periaqueductal grey matter
Stress
description Rationale: Previous studies suggested that the dorsal column of the periaqueductal grey matter (dPAG) can be a target of neural pathways from hypothalamic nuclei involved in triggering fear-related defensive responses. In turn, evidence is provided suggesting that microinjection of the nitric oxide (NO) donor SIN-1 into the anterior hypothalamus (AH) of mice evokes panic-like behaviours and fear-induced antinociception. However, it is unknown whether the dPAG of mice mediates these latter defensive responses organised by AH neurons. Objectives: This study was designed to examine the role of dPAG in mediating SIN-1-evoked fear-induced defensive behavioural and antinociceptive responses organised in the AH of mice. Methods: First, neural tract tracing was performed to characterise the AH-dPAG pathways. Then, using neuropharmacological approaches, we evaluated the effects of dPAG pretreatment with either the non-selective synaptic blocker cobalt chloride (CoCl2; 1 mM/0.1 μL) or the competitive N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (0.1 nmol/0.1 μL) on defensive behaviours and antinociception induced by microinjections of SIN-1 in the AH of male C57BL/6 mice. Results: AlexaFluor488-conjugated dextran-labelled axonal fibres from AH neurons were identified in both dorsomedial and dorsolateral PAG columns. Furthermore, we showed that pre-treatment of the dPAG with either CoCl2 or LY235959 inhibited freezing and impaired oriented escape and antinociception induced by infusions of SIN-1 into the AH. Conclusions: These findings suggest that the panic-like freezing and oriented escape defensive behaviours, and fear-induced antinociception elicited by intra-AH microinjections of SIN-1 depend on the activation of dPAG NMDA receptors.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:37:43Z
2023-07-29T13:37:43Z
2023-02-01
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/10.1007/s00213-023-06309-7
Psychopharmacology, v. 240, n. 2, p. 319-335, 2023.
1432-2072
0033-3158
http://hdl.handle.net/11449/248215
10.1007/s00213-023-06309-7
2-s2.0-85146383559
url http://dx.doi.org/10.1007/s00213-023-06309-7
http://hdl.handle.net/11449/248215
identifier_str_mv Psychopharmacology, v. 240, n. 2, p. 319-335, 2023.
1432-2072
0033-3158
10.1007/s00213-023-06309-7
2-s2.0-85146383559
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Psychopharmacology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 319-335
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
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