Systemic 8-OH-DPAT challenge causes hyperventilation largely via activating pre-botzinger complex 5-HT1A receptors.

Abstract

Systemic 8-OH-DPAT (a 5-HT1A receptor agonist) challenge evokes hyperventilation independent of peripheral 5-HT1A receptors. Though the pre-Botzinger Complex (PBC) is critical in generating respiratory rhythm and activation of local 5-HT1A receptors induces tachypnea via disinhibition of local GABAA neurons, its role in the respiratory response to systemic 8-OH-DPAT challenge is still unclear. In anesthetized rats, 8-OH-DPAT (100 μg/kg, iv) was injected twice to confirm the reproducibility of the evoked responses. The same challenges were performed after bilateral microinjections of (S)-WAY-100135 (a 5-HT1A receptor antagonist) or gabazine (a GABAA receptor antagonist) into the PBC. Our results showed that: 1) 8-OH-DPAT caused reproducible hyperventilation associated with hypotension and bradycardia; 2) microinjections of (S)-WAY-100135 into the PBC attenuated the hyperventilation by ˜60 % without effect on the evoked hypotension and bradycardia; and 3) the same hyperventilatory attenuation was also observed after microinjections of gabazine into the PBC. Our data suggest that PBC 5-HT1A receptors play a key role in the respiratory response to systemic 8-OH-DPAT challenge likely via disinhibiting local GABAergic neurons.

• Authors: Jianguo Zhuang, Fadi Xu
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 296 Pg. 103810 (02 2022) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 34728431 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• GABA Antagonists
• Piperazines
• Pyridazines
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• WAY 100135
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• gabazine

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (administration & dosage, pharmacology)
• Animals
• Disease Models, Animal
• GABA Antagonists (pharmacology)
• Hyperventilation (chemically induced, drug therapy)
• Male
• Medulla Oblongata (drug effects, metabolism)
• Piperazines (pharmacology)
• Pyridazines (pharmacology)
• Rats
• Receptor, Serotonin, 5-HT1A (drug effects, physiology)
• Respiratory Center (drug effects, metabolism)
• Serotonin 5-HT1 Receptor Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)