5-Hydroxytryptamine1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception

被引：32

作者：

Biagioni, Audrey Franceschi ^{[1
,2
]}

de Oliveira, Rithiele Cristina ^{[1
,2
,5
]}

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, Helio, Jr. ^{[2
,3
,4
]}

Coimbra, Norberto Cysne ^{[1
,2
,3
]}

机构：

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

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

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

来源：

EUROPEAN NEUROPSYCHOPHARMACOLOGY | 2016年 / 26卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

Panic-like behaviour; Antinociception-5-HTiA receptor; Dorsomediat hypothlamus; Dorsal raphe nucleus outputs; Biotinylated dextran amine neurotracer; PERIAQUEDUCTAL GRAY-MATTER; SEROTONIN-CONTAINING NEURONS; CENTRAL-NERVOUS-SYSTEM; ELECTRICAL-STIMULATION; ASCENDING PROJECTIONS; GABA(A) RECEPTOR; 5-HT2; RECEPTORS; PANIC DISORDER; AUTORADIOGRAPHIC ANALYSIS; REGIONAL-DISTRIBUTION;

D O I：

10.1016/j.euroneuro.2015.12.032

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：532 / 545

页数：14

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