Behavioral Arrest and a Characteristic Slow Waveform Are Hallmark Responses to Selective 5-HT2A Receptor Activation

Authors

April Contreras, University of Nevada, Las Vegas
Matthew Khumnark, University of Nevada, Las Vegas
Rochelle M. Hines, University of Nevada, Las VegasFollow
Dustin J. Hines, University of Nevada, Las VegasFollow

Document Type

Article

Publication Date

1-21-2021

Publication Title

Scientific Reports

Volume

11

Issue

1

First page number:

1

Last page number:

12

Abstract

© 2021, The Author(s). 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.

Disciplines

Molecular and Cellular Neuroscience

File Format

pdf

File Size

11298 KB

Language

English

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Repository Citation

Contreras, A., Khumnark, M., Hines, R., Hines, D. (2021). Behavioral Arrest and a Characteristic Slow Waveform Are Hallmark Responses to Selective 5-HT2A Receptor Activation. Scientific Reports, 11(1), 1-12.
http://dx.doi.org/10.1038/s41598-021-81552-6