Altmetric

The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner.

File Description SizeFormat 
JOP-2019-4055.R1_Proof_hi.pdfAccepted version1.05 MBAdobe PDFView/Open
Title: The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner.
Authors: Buchborn, T
Lyons, T
Song, C
Feilding, A
Knöpfel, T
Item Type: Journal Article
Abstract: BACKGROUND: Serotonin 2A receptors, the molecular target of psychedelics, are expressed by neuronal and vascular cells, both of which might contribute to brain haemodynamic characteristics for the psychedelic state. AIM: Aiming for a systemic understanding of psychedelic vasoactivity, here we investigated the effect of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine - a new-generation agonist with superior serotonin 2A receptor selectivity - on brain-supplying neck-arterial blood flow. METHODS: We recorded core body temperature and employed non-invasive, collar-sensor based pulse oximetry in anesthetised mice to extract parameters of local blood perfusion, oxygen saturation, heart and respiration rate. Hypothesising an overlap between serotonergic pulse- and thermoregulation, recordings were done under physiological and elevated pad temperatures. RESULTS: N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (1.5 mg/kg, subcutaneous) significantly increased the frequency of heart beats accompanied by a slight elevation of neck-arterial blood flow. Increasing the animal-supporting heat-pad temperature from 37°C to 41°C enhanced the drug's effect on blood flow while counteracting tachycardia. Additionally, N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine promoted bradypnea, which, like tachycardia, quickly reversed at the elevated pad temperature. The interrelatedness of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine's respiro-cardiovascular effects and thermoregulation was further corroborated by the drug selectively increasing the core body temperature at the elevated pad temperature. Arterial oxygen saturation was not affected by N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine at either temperature. CONCLUSIONS: Our findings imply that selective serotonin 2A receptor activation modulates systemic cardiovascular functioning in orchestration with thermoregulation and with immediate relevance to brain-imminent neck (most likely carotid) arteries. As carotid branching is a critical last hub to channel cardiovascular output to or away from the brain, our results might have implications for the brain haemodynamics associated with psychedelia.
Issue Date: 12-Feb-2020
Date of Acceptance: 1-Feb-2020
URI: http://hdl.handle.net/10044/1/76920
DOI: 10.1177/0269881120903465
ISSN: 0269-8811
Publisher: SAGE Publications
Journal / Book Title: Journal of Psychopharmacology
Copyright Statement: © The Author(s) 2020. The final, definitive version of this paper has been published in Buchborn, T., Lyons, T., Song, C., Feilding, A., & Knöpfel, T. (2020). The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner. Journal of Psychopharmacology by Sage Publications Ltd. All rights reserved. It is available at: https://doi.org/10.1177/0269881120903465
Sponsor/Funder: European Commission
Keywords: 25CN-NBOH
bradypnea
carotid artery
haemodynamics
hypertension
psychedelic
selective 5-HT2AR agonist
tachycardia
thermoregulation
vasoactive
25CN-NBOH
bradypnea
carotid artery
haemodynamics
hypertension
psychedelic
selective 5-HT2AR agonist
tachycardia
thermoregulation
vasoactive
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Psychiatry
Publication Status: Published online
Conference Place: United States
Online Publication Date: 2020-02-12
Appears in Collections:Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons