Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways

被引：44
|
作者：
Biagioni, Audrey Francisco [1 ,2 ,3 ]
de Freitas, Renato Leonardo [1 ,2 ,3 ]
da Silva, Juliana Almeida [1 ,2 ,3 ]
de Oliveira, Rithiele Cristina [1 ,3 ]
de Oliveira, Ricardo [1 ,3 ]
Alves, Vani Maria [1 ]
Coimbra, Norberto Cysne [1 ,2 ,3 ]
机构：
[1] FMRP USP, Dept Farmacol, Lab Neuroanat & Neuropsicobiol, BR-14049900 Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, INeC, BR-14040901 Ribeirao Preto, SP, Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, NAP USP Neurobiol Emocoes NuPNE, BR-14049900 Ribeirao Preto, SP, Brazil
来源：
NEUROPHARMACOLOGY | 2013年 / 67卷
基金：
巴西圣保罗研究基金会;
关键词：
Defensive behaviour; Fear-induced antinociception; Dorsomedial hypothalamus; Serotonin-mediated neurotransmission; Dorsal raphe nucleus; Locus coeruleus; PERIAQUEDUCTAL GRAY-MATTER; RATTUS-NORVEGICUS RODENTIA; ELECTRICAL-STIMULATION; SUPERIOR COLLICULUS; MEDIAN RAPHE; LATERAL HYPOTHALAMUS; CHEMICAL-STIMULATION; INFERIOR COLLICULUS; GENERALIZED ANXIETY; RECEPTOR BLOCKADE;
D O I：
10.1016/j.neuropharm.2012.10.024
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Decrease of gamma-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain. inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABA(A) receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABA(A) receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT2A/2C receptor antagonist ketanserin and the 5-HT2A receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABA(A) receptor blockade in the DMH. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码：379 / 394
页数：16
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