Serotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT2A/2C receptors to modulate the post-ictal antinociception

Author(s)

Freitas, Renato Leonardo ^{[1, 2]} ; Bassi, Gabriel Shimizu ^{[1, 2]} ; de Oliveira, Ana Maria ^[3] ; Coimbra, Norberto Cysne ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Neurocience & Behav, BR-14049901 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Ribeirao Preto, Dept Chem & Phys, Pharmacol Lab, BR-14049903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Experimental Neurology; v. 213, n. 2, p. 410-418, OCT 2008.
• Web of Science Citations: 26

Abstract

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. Pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl- influx antagonist, was peripherally used to induce tonic-clonic seizures in Wistar rats. The nociceptive threshold was measured by the tail-flick test. Neurochemical lesions of the DRN, performed with microinjection of ibotenic acid (1.0 mu g/0.2 mu L), caused a significant decrease of tonic-clonic seizure-induced antinociception, suggesting the involvement of this nucleus in this antinociceptive Process. Microinjections of methysergide (1.0 and 5.0 mu g/0.2 mu L), a non-selective serotonergic receptor antagonist, into DRN caused a significant decrease in the post-ictal antinociception in seizing animals, compared to controls, in all post-ictal periods Presently studied. These findings were corroborated by microinjections of ketanserin (at 1.0 and 5.0 mu g/0.2 mu L) into DRN. Ketanserin is an antagonist with large affinity for 5-HT2A/2C serotonergic receptors, which, in this Case, Caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT2A/2C receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures. (c) 2008 Elsevier Inc, All rights reserved. (AU)