Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI.

Randall J. Olson; Lowell Bartlett; Alex Sonneborn; Russell Milton; Zachary Bretton-Granatoor; Ayesha Firdous; Alexander Z Harris; Atheir I. Abbas

doi:10.1016/j.neuropharm.2024.110030

Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI.

Randall J. Olson, Lowell Bartlett, Alex Sonneborn, Russell Milton, Zachary Bretton-Granatoor, Ayesha Firdous, Alexander Z Harris, Atheir I. Abbas

Neuropharmacology October 1, 2024 DOI: 10.1016/j.neuropharm.2024.110030 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Experimental study Peer reviewed
Population	Male mice
Interventions	2 5-Dimethoxy-4-iodoamphetamine (DOI)
Topics	Serotonin
Keywords	Behavioral state Doi Delta Desynchronization Gamma Hallucinogen Prefrontal cortex Psychedelic
Citations	3
Key findings	The psychedelic DOI induces persistent desynchronization in the medial prefrontal cortex, including during rest when synchronized activity is typical.

Abstract

Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving male mice after administration of the 5-HT2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results suggest that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.

Comparable studies

Other preclinical and animal studies on serotonin, most cited first.

Study	Year	Design
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice	2021	Observational cohort
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context)	1987	Experimental study
Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models	2023	Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain	1987	Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells	2006	In vitro laboratory study

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