title: Serotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT(2A/2C) receptors to modulate the post-ictal antinociception.
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 microg/0.2 microL), 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 microg/0.2 microL), 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 microg/0.2 microL) into DRN. Ketanserin is an antagonist with large affinity for 5-HT(2A/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-HT(2A/2C) receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures.
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Renato Leonardo
authors.initials: RL
authors.lastname: Freitas
authors.forename: Gabriel Shimizu
authors.initials: GS
authors.lastname: Bassi
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Oliveira
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin