Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats
Nicolas G. Glynos, Emma R. Huels, Trent Groenhout, Ashley L. B. Raghu, Amanda Nelson, Youngsoo Kim, Abdallah M. Zeid, Tiecheng Liu, George A. Mashour, Robert T. Kennedy, Dinesh Pal
Journal of Neuroscience December 19, 2025 DOI: 10.1523/jneurosci.0742-24.2025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female adult rats |
| Interventions | N N-Dimethyltryptamine (DMT) |
| Dose | 0.75, 3.75, 7.5 mg/kg |
| Topics | Serotonin 5-MeO-DMT DMT |
| Keywords | Neurochemical Dopamine Neurophysiology Somatosensory system Prefrontal cortex Electroencephalography Neurotransmitter Neuropharmacology Neurochemistry |
| Citations | 11 |
| Key findings | DMT produces dose-dependent increases in cortical serotonin and dopamine, alters EEG spectral power across multiple frequency bands, and endogenous DMT was detected in the cortex of most rats at baseline. |
Abstract
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated for the treatment of psychiatric disorders. Although the neurophysiological effects of DMT in humans are well characterized, similar studies in animal models and data on the neurochemical effects of DMT are generally lacking, which are critical for a mechanistic understanding. Here, we combined behavioral analysis, high-density (32-channel) electroencephalography, and ultrahigh-performance liquid chromatography-tandem mass spectrometry to simultaneously quantify changes in behavior, cortical neural dynamics, and levels of 17 neurochemicals in medial prefrontal and somatosensory cortices before, during, and after intravenous administration of DMT (0.75, 3.75, 7.5 mg/kg) in male and female adult rats. All three doses of DMT produced head twitch response with most twitches observed after the low dose. DMT caused dose-dependent increases in serotonin and dopamine levels in both cortical sites, a reduction in EEG spectral power in theta (4-10 Hz) and low gamma (25-55 Hz), and an increase in spectral power in delta (1-4 Hz), medium gamma (65-115 Hz), and high gamma (125-155 Hz) bands. Functional connectivity decreased in the delta band and increased across the gamma bands. We detected cortical DMT in baseline wake condition in 70-80% of the animals tested at levels comparable to serotonin and dopamine, which, together with a previous study in the occipital cortex, motivates cross-species studies to confirm endogenous presence of DMT. This study represents one of the most comprehensive characterizations of psychedelic drug action in rats and the first to be conducted with intravenous DMT.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |
Citations in the library
Cited by 2
Cites 38
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- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Broadband Cortical Desynchronization Underlies the Human Psychedelic State Journal of Neuroscience September 18, 2013
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release Brain Research April 1, 1999
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