The 5-HT2AR agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner

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Title: The 5-HT2AR 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
Knopfel, T
Item Type: Journal Article
Abstract: Background: Serotonin 2A receptors (5-HT2ARs), the molecular target of psychedelics, are expressed by neuronal and vascular cells, both of which might contribute to the brain haemodynamics characteristic for the psychedelic state. Aim: Aiming for a systemic understanding of psychedelic vasoactivity, we here investigated the effect of 25CN-NBOH (N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine) —a new-generation agonist with superior 5-HT2AR selectivity— on brain-supplying neck-arterial blood flow. Methods: We recorded body core 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 temperature. Results: 25CN-NBOH (1.5 mg/kg, s.c.) 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 to 41 ̊C enhanced the drug’s effect on blood flow while counteracting tachycardia. Additionally, 25CN-NBOH promoted bradypnea, which like tachycardia quickly reversed at elevated pad temperature. The interrelatedness of 25CN-NBOH’s respiro-cardiovascular effects to thermoregulation was further corroborated by the drug selectively increasing body core temperature at elevated pad temperature. Arterial oxygen saturation at neither temperature was affected by 25CN-NBOH. Conclusions: Our findings imply that selective 5-HT2AR 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.
Date of Acceptance: 29-Dec-2019
ISSN: 0269-8811
Publisher: SAGE Publications
Journal / Book Title: Journal of Psychopharmacology
Copyright Statement: This paper is embargoed until publication.
Sponsor/Funder: European Commission
Commission of the European Communities
Funder's Grant Number: 703143
Keywords: 11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:Faculty of Medicine

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