5-HT1A/1B, 5-HT6, and 5-HT7 serotonergic receptors recruitment in tonic-clonic seizure-induced antinociception: Role of dorsal raphe nucleus

被引：34

作者：

Freitas, Renato Leonardo ^{[1
,5
]}

dos Reis Ferreira, Celio Marcos ^{[1
,4
]}

Castiblanco Urbina, Maria Angelica ^{[1
]}

Marino, Andres Uribe ^{[1
]}

Carvalho, Andressa Daiane ^{[1
,5
]}

Butera, Giuseppe ^{[1
,3
]}

de Oliveira, Ana Maria ^{[2
]}

Coimbra, Norberto Cysne ^{[1
,5
]}

机构：

[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Lab Neuroanat & Neuropsicobiol, BR-14049900 Ribeirao Preto, SP, Brazil

[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, Farmacol Lab, BR-14040903 Ribeirao Preto, SP, Brazil

[3] Univ Fed Mato Grosso do Sul, BR-79070900 Campo Grande, MS, Brazil

[4] Ctr Univ Patos de Minas, Dept Fisiote, BR-38702054 Patos De Minas, MG, Brazil

[5] Univ Sao Paulo, INeC, BR-14040901 Ribeirao Preto, SP, Brazil

来源：

EXPERIMENTAL NEUROLOGY | 2009年 / 217卷 / 01期

基金：

巴西圣保罗研究基金会;

关键词：

GABA-A receptor; Pentylenetetrazole-induced tonic-clonic seizures; Antinociception; 5-hydroxytryptamine; 5-HT1A/1B receptors; 5-HT6; receptors; 5-HT7; Dorsal raphe nucleus; Pain; Epilepsy; POST-ICTAL ANALGESIA; RAT-BRAIN CORTEX; 5-HYDROXYTRYPTAMINE RELEASE; SPINAL-CORD; IMMUNOHISTOCHEMICAL EVIDENCE; AUTORADIOGRAPHIC EVIDENCE; BINDING-SITES; HORN NEURONS; CELL-BODIES; ADULT-RAT;

D O I：

10.1016/j.expneurol.2009.01.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Pharmacological studies have been focused on the involvement of different neural pathways in the organization of antinociception that follows tonic-clonic seizures, including 5-hydroxytryptamine (5-HT)-, norepinephrine-, acetylcholine- and endogenous opioid peptide-mediated mechanisms, giving rise to more in-depth comprehension of this interesting post-ictal antinociceptive phenomenon. The present work investigated the involvement of 5-HT1A/1B, 5-HT6, and 5-HT7 serotonergic receptors through peripheral pretreatment with methiothepin at doses of 0.5, 1.0, 2.0 and 3.0 mg/kg in the organization of the post-ictal antinociception elicited by pharmacologically (with pentylenetetrazole at 64 mg/kg)-induced tonic-clonic seizures. Methiothepin at 1.0 mg/kg blocked the post-ictal antinociception recorded after the end of seizures, whereas doses of 2.0 and 3.0 mg/kg potentiated the post-ictal antinociception. The nociceptive thresholds were kept higher than those of the control group. However, when the same 5-hydroxytryptamine receptors antagonist was microinjected (at 1.0, 3.0 and 5.0 mu g/0.2 mu L) in the dorsal raphe nucleus, a mesencephalic structure rich in serotonergic neurons and 5-HT receptors, the post-ictal hypo-analgesia was consistently antagonized. The present findings suggest a dual effect of methiothepin, characterized by a disinhibitory effect on the post-ictal antinociception when peripherally administered (possibly due to an antagonism of pre-synaptic 5-HT1A serotonergic autoreceptors in the pain endogenous inhibitory system) and an inhibitory effect (possibly due to a DRN post-synaptic 5-HT1B, 5-HT6, and 5-HT7 serotonergic receptors blockade) when centrally administered. The present data also Suggest that serotonin-mediated mechanisms of the dorsal raphe nucleus exert a key-role in the modulation of the post-ictal antinociception. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：16 / 24

页数：9

共 55 条

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