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

Author(s)

Freitas, Renato Leonardo ^{[1, 2]} ; dos Reis Ferreira, Celio Marcos ^{[1, 3]} ; Castiblanco Urbina, Maria Angelica ^[1] ; Marino, Andres Uribe ^[1] ; Carvalho, Andressa Daiane ^{[1, 2]} ; Butera, Giuseppe ^{[1, 4]} ; de Oliveira, Ana Maria ^[5] ; Coimbra, Norberto Cysne ^{[1, 2]}

Affiliation

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

^[2] Univ Sao Paulo, INeC, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Ctr Univ Patos de Minas, Dept Fisiote, BR-38702054 Patos De Minas, MG - Brazil

^[4] Univ Fed Mato Grosso do Sul, BR-79070900 Campo Grande, MS - Brazil

^[5] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, Farmacol Lab, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Experimental Neurology; v. 217, n. 1, p. 16-24, MAY 2009.
• Web of Science Citations: 27

Abstract

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-HT(1A/1B), 5-HT(6), and 5-HT(7) 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-HT(1A) serotonergic autoreceptors in the pain endogenous inhibitory system) and an inhibitory effect (possibly due to a DRN post-synaptic 5-HT(1B), 5-HT(6), and 5-HT(7) 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. (AU)