Journal Article

5-HT receptors exert differential effects on seizure-induced respiratory arrest in DBA/1 mice

Pan, Yundan, Guo, Jialing, Feng, Hua-Jun, Tan, Zheren

2024

Overview

Both clinical and animal studies demonstrated that seizure-induced respiratory arrest (S-IRA) contributes importantly to sudden unexpected death in epilepsy (SUDEP). It has been shown that enhancing serotonin (5-HT) function relieves S-IRA in animal models of SUDEP, including DBA/1 mice. Direct activation of 5-HT 3 and 5-HT 4 receptors suppresses S-IRA in DBA/1 mice, indicating that these receptors are involved in S-IRA. However, it remains unknown if other subtypes of 5-HT receptors are implicated in S-IRA in DBA/1 mice. In this study, we investigated the action of an agonist of the 5-HT 1A (8-OH-DPAT), 5-HT 2A (TCB-2), 5-HT 2B (BW723C86), 5-HT 2C (MK-212), 5-HT 6 (WAY-208466) and 5-HT 7 (LP-211) receptor on S-IRA in DBA/1 mice. An agonist of the 5-HT receptor or a vehicle was intraperitoneally administered 30 min prior to acoustic simulation, and the effect of each drug/vehicle on the incidence of S-IRA was videotaped for offline analysis. We found that the incidence of S-IRA was significantly reduced by TCB-2 at 10 mg/kg (30%, n = 10; p < 0.01, Fisher’s exact test) but was not altered by other agonists compared with the corresponding vehicle controls in DBA/1 mice. Our data demonstrate that 5-HT 2A receptors are implicated in S-IRA, and 5-HT 1A , 5-HT 2B , 5-HT 2C , 5-HT 6 and 5-HT 7 receptors are not involved in S-IRA in DBA/1 mice.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 8-Hydroxy-2-(di-n-propylamino)tetralin / Acoustic simulation / Acoustics / Agonists / Animal models / Animals / Convulsions & seizures / Disease Models, Animal / Drug dosages / Epilepsy / Laboratory animals / Male / Mice / Mice, Inbred DBA / Neurophysiology / Receptors / Receptors, Serotonin - metabolism / Seizures / Seizures - metabolism / Serotonin / Serotonin Receptor Agonists - pharmacology / Serotonin S1 receptors / Serotonin S2 receptors / Serotonin S3 receptors / Serotonin S4 receptors / Serotonin S6 receptors / Serotonin S7 receptors / Software / Sudden Unexpected Death in Epilepsy - etiology / Ventilators