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The role of dorsomedial and ventrolateral columns of the periaqueductal gray matter and in situ 5‐HT 2A and 5‐HT 2C serotonergic receptors in post‐ictal antinociception
Author(s) -
Freitas Renato Leonardo,
Oliveira Rithiele Cristina,
Oliveira Ricardo,
PaschoalinMaurin Tatiana,
Aguiar Corrêa Fernando Morgan,
Coimbra Norberto Cysne
Publication year - 2014
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21697
Subject(s) - serotonergic , chemistry , methysergide , periaqueductal gray , 5 ht receptor , antagonist , ketanserin , neurotransmission , receptor antagonist , pharmacology , serotonin , receptor , neuroscience , medicine , endocrinology , psychology , central nervous system , biochemistry , midbrain
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 CoCl 2 /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‐HT 2A/2C receptors, decreased tonic‐clonic seizure‐induced antinociception. Both dmPAG and vlPAG treatment with either the 5‐HT 2A receptor selective antagonist R‐96544 (10 nM/0.2 µL), or the 5‐HT 2C 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‐HT 2A and 5‐HT 2C serotonergic receptors in dmPAG and vlPAG columns, plays a critical role in the elaboration of post‐ictal antinociception. Synapse, 68:16–30, 2014 . © 2013 Wiley Periodicals, Inc.