Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation

Abstract Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinoge...

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Autores principales:	April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29bbe2b5088042c99a1065f444c8bf2f
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spelling	oai:doaj.org-article:29bbe2b5088042c99a1065f444c8bf2f2021-12-02T13:48:41ZBehavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation10.1038/s41598-021-81552-62045-2322https://doaj.org/article/29bbe2b5088042c99a1065f444c8bf2f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81552-6https://doaj.org/toc/2045-2322Abstract Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we observe a disorganization of behavior which includes frequent episodes of behavioral arrest that consistently precede the HTR by a precise interval. By combining behavioral analysis with electroencephalogram (EEG) recordings we describe a characteristic pattern composed of two distinctive EEG waveforms, Phase 1 and Phase 2, that map onto behavioral arrest and the HTR respectively, with the same temporal separation. Phase 1, which underlies behavioral arrest, is a 3.5–4.5 Hz waveform, while Phase 2 is slower at 2.5–3.2 Hz. Nicotine pretreatment, considered an integral component of ritualistic hallucinogen practices, attenuates 25I-NBOH induced HTR and Phase 2 waveforms, yet increases behavioral arrest and Phase 1 waveforms. Our results suggest that in addition to the HTR, behavioral arrest and characteristic meso level slow waveforms are key hallmarks of the response to 5-HT2AR activation. Increased understanding of the response to serotonergic hallucinogens may provide mechanistic insights into perception and hallucinations, as well as regulation of mood.April ContrerasMatthew KhumnarkRochelle M. HinesDustin J. HinesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q April Contreras Matthew Khumnark Rochelle M. Hines Dustin J. Hines Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
description	Abstract Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we observe a disorganization of behavior which includes frequent episodes of behavioral arrest that consistently precede the HTR by a precise interval. By combining behavioral analysis with electroencephalogram (EEG) recordings we describe a characteristic pattern composed of two distinctive EEG waveforms, Phase 1 and Phase 2, that map onto behavioral arrest and the HTR respectively, with the same temporal separation. Phase 1, which underlies behavioral arrest, is a 3.5–4.5 Hz waveform, while Phase 2 is slower at 2.5–3.2 Hz. Nicotine pretreatment, considered an integral component of ritualistic hallucinogen practices, attenuates 25I-NBOH induced HTR and Phase 2 waveforms, yet increases behavioral arrest and Phase 1 waveforms. Our results suggest that in addition to the HTR, behavioral arrest and characteristic meso level slow waveforms are key hallmarks of the response to 5-HT2AR activation. Increased understanding of the response to serotonergic hallucinogens may provide mechanistic insights into perception and hallucinations, as well as regulation of mood.
format	article
author	April Contreras Matthew Khumnark Rochelle M. Hines Dustin J. Hines
author_facet	April Contreras Matthew Khumnark Rochelle M. Hines Dustin J. Hines
author_sort	April Contreras
title	Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
title_short	Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
title_full	Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
title_fullStr	Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
title_full_unstemmed	Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
title_sort	behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-ht2a receptor activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29bbe2b5088042c99a1065f444c8bf2f
work_keys_str_mv	AT aprilcontreras behavioralarrestandacharacteristicslowwaveformarehallmarkresponsestoselective5ht2areceptoractivation AT matthewkhumnark behavioralarrestandacharacteristicslowwaveformarehallmarkresponsestoselective5ht2areceptoractivation AT rochellemhines behavioralarrestandacharacteristicslowwaveformarehallmarkresponsestoselective5ht2areceptoractivation AT dustinjhines behavioralarrestandacharacteristicslowwaveformarehallmarkresponsestoselective5ht2areceptoractivation
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Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation

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