title: The role of dorsomedial and ventrolateral columns of the periaqueductal gray matter and in situ 5-HT₂A and 5-HT₂C serotonergic receptors in post-ictal antinociception.
abstract: The periaqueductal gray matter (PAG) consists in a brainstem structure rich in 5-hydroxytryptamine (5-HT) inputs related to the modulation of pain. The involvement of each of the serotonergic receptor subtypes found in PAG columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, regarding post-ictal antinociception have not been elucidated. The present work investigated the participation of the dmPAG and vlPAG columns in seizure-induced antinociception. Specifically, we studied the involvement of serotonergic neurotransmission in these columns on antinociceptive responses that follow tonic-clonic epileptic reactions induced by pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl(-) influx antagonist. Microinjections of cobalt chloride (1.0 mM CoCl2 /0.2 µL) into the dmPAG and vlPAG caused an intermittent local synaptic inhibition and decreased post-ictal antinociception that had been recorded at various time points after seizures. Pretreatments of the dmPAG or the vlPAG columns with the nonselective serotonergic receptors antagonist methysergide (5.0 µg/0.2 µL) or intramesencephalic microinjections of ketanserin (5.0 µg/0.2 µL), a serotonergic antagonist with more affinity to 5-HT2A/2C receptors, decreased tonic-clonic seizure-induced antinociception. Both dmPAG and vlPAG treatment with either the 5-HT2A receptor selective antagonist R-96544 (10 nM/0.2 µL), or the 5-HT2C receptors selective antagonist RS-102221 (0.15 µg/0.2 µL) also decrease post-ictal antinociception. These findings suggest that serotonergic neurotransmission, which recruits both 5-HT2A and 5-HT2C serotonergic receptors in dmPAG and vlPAG columns, plays a critical role in the elaboration of post-ictal antinociception.
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Av. dos Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil; Institute for Neuroscience and Behavior (INeC), Av. do Café, S/N, Ribeirão Preto (SP), Brazil.
authors.forename: Renato Leonardo
authors.initials: RL
authors.lastname: de Freitas
authors.forename: Rithiele Cristina
authors.initials: RC
authors.lastname: de Oliveira
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Oliveira
authors.forename: Tatiana
authors.initials: T
authors.lastname: Paschoalin-Maurin
authors.forename: Fernando Morgan
authors.initials: FM
authors.lastname: de Aguiar Corrêa
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D008297:Male; D059225:Nociception; D009928:Organ Specificity; D010487:Periaqueductal Gray / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D059326:Serotonergic Neurons / Q000378:metabolism / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: 5-HT2A and 5-HT2C serotonergic receptors; GABA-A receptors; periaqueductal gray matter; postictal antinociception; tonic-clonic seizures