5-Hydroxytryptamine(1A) receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception

Author(s)

Biagioni, Audrey Franceschi ^{[1, 2]} ; de Oliveira, Rithiele Cristina ^{[1, 2, 3]} ; de Oliveira, Ricardo ^{[1, 2]} ; da Silva, Juliana Almeida ^{[1, 2]} ; dos Anjos-Garcia, Taylion ^{[1, 2]} ; Roncon, Camila Marroni ^{[1, 2]} ; Corrado, Alexandre Pinto ^[1] ; Zangrossi, Jr., Helio ^{[2, 4, 5]} ; Coimbra, Norberto Cysne ^{[1, 2, 4]}

Affiliation

^[1] Univ Sao Paulo FMRP USP, Ribeirao Preto Sch Med, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, Ave Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

^[2] Behav Neurosci Inst INeC, Ave Cafe 2450, BR-14050220 Sao Paulo - Brazil

^[3] Univ Fed Mato Grosso, Med Sch UFMT, Ave Alexandre Ferronato, 1200, Reserva 35, Setor Ind, BR-78550000 Sinop, MG - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, NAP USP Neurobiol Emot Res Ctr NuPNE, Ave Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuropsychopharmacol, Ave Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 26, n. 3, p. 532-545, MAR 2016.
• Web of Science Citations: 17

Abstract

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT(1A) receptor-labelled neurons in the MH. Moreover, the effects of pretreatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A, receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABA(A) receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT(1A) receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5HT(1A) DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH. (C) 2015 Elsevier B.V. and ECNP. All rights reserved. (AU)

• FAPESP's process: 11/09850-1 - study of serotoninergic pathways that connect the dorsal raphe nucleus to the Lateral Septal Area on the Modulation of Defensive Behavior Organized by periaqueductal gray performed by the prefrontal cortex
• Grantee: Ricardo de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/10742-7 - Paresthesia as a new approach of study for panic disorder: basic and clinical research
• Grantee: Audrey Franceschi Biagioni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 08/08955-1 - Involvement of the Dorsal Raphe Nucleus Neural Networks and Serotonergic Neurotransmittion in the Locus Coeruleus in Antinociceptive Processess Induced by Oriented Escape Reaction Evoked by Chemical Stimulation of the Medial Hypothalamus.
• Grantee: Audrey Franceschi Biagioni
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/23238-0 - Evaluation of cooperative mechanisms between opioidergic and serotonergic systems in the dorsal periaqueductal grey matter in the antidepressants effects
• Grantee: Camila Marroni Roncon
• Support Opportunities: Scholarships in Brazil - Post-Doctoral