Journal article
5-HT2A receptor activation is necessary for CO2-induced arousal
Journal of neurophysiology, Vol.114(1), pp.233-243
07/2015
DOI: 10.1152/jn.00213.2015
PMCID: PMC4507958
PMID: 25925320
Abstract
Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive sleep apnea and sudden unexpected death in epilepsy. Serotonin (5-HT) plays a significant role in hypercapnia-induced arousal. The mechanism of 5-HT's role in this protective response is unknown. Here we sought to identify the specific 5-HT receptor subtype(s) involved in this response. Wild-type mice were pretreated with antagonists against 5-HT receptor subtypes, as well as antagonists against adrenergic, cholinergic, histaminergic, dopaminergic, and orexinergic receptors before challenge with inspired CO2 or hypoxia. Antagonists of 5-HT(2A) receptors dose-dependently blocked CO2-induced arousal. The 5-HT(2C) receptor antagonist, RS-102221, and the 5-HT1A receptor agonist, 8-OH-DPAT, attenuated but did not completely block CO2-induced arousal. Blockade of non-5-HT receptors did not affect CO2-induced arousal. None of these drugs had any effect on hypoxia-induced arousal. 5-HT2 receptor agonists were given to mice in which 5-HT neurons had been genetically eliminated during embryonic life (Lmx1b(f/f/p)) and which are known to lack CO2-induced arousal. Application of agonists to 5-HT(2A), but not 5-HT(2C), receptors, dose-dependently restored CO2-induced arousal in these mice. These data identify the 5-HT(2A) receptor as an important mediator of CO2-induced arousal and suggest that, while 5-HT neurons can be independently activated to drive CO2-induced arousal, in the absence of 5-HT neurons and endogenous 5-HT, 5-HT receptor activation can act in a permissive fashion to facilitate CO2-induced arousal via another as yet unidentified chemosensor system.
Details
- Title: Subtitle
- 5-HT2A receptor activation is necessary for CO2-induced arousal
- Creators
- Gordon F Buchanan - Department of Neurology, Yale University, New Haven, Connecticut; Veteran's Affairs Medical Center, West Haven, Connecticut; Department of Neurology, University of Iowa, Iowa City, Iowa; gordon-buchanan@uiowa.eduHaleigh R Smith - Department of Neurology, Yale University, New Haven, ConnecticutAmanda MacAskill - University of Glasgow School of Medicine, Glasgow, Scotland, United KingdomGeorge B Richerson - Department of Neurology, Yale University, New Haven, Connecticut; Department of Neurology, University of Iowa, Iowa City, Iowa; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa; and Veteran's Affairs Medical Center, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of neurophysiology, Vol.114(1), pp.233-243
- DOI
- 10.1152/jn.00213.2015
- PMID
- 25925320
- PMCID
- PMC4507958
- NLM abbreviation
- J Neurophysiol
- ISSN
- 0022-3077
- eISSN
- 1522-1598
- Publisher
- United States
- Grant note
- K08 NS069667 / NINDS NIH HHS K08-NS-069667 / NINDS NIH HHS R01-HD-052772 / NICHD NIH HHS P20-NS-076916 / NINDS NIH HHS U01 NS090414 / NINDS NIH HHS
- Language
- English
- Date published
- 07/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984018933202771
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