N,N‐Dimethyltryptamine ( DMT ) Acutely Exposed to Mouse Ventral Tegmental Area I h ‐Negative Neurons Alters the Firing Rate and Conductance in a Sex‐Dependent Manner
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen, Kristi A. Kohlmeier
Journal of Neurochemistry May 1, 2026 DOI: 10.1111/jnc.70463 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Ex vivo study Peer reviewed |
|---|---|
| Population | I_h-negative neurons from male and female mouse ventral tegmental area |
| Intervention | DMT |
| Dose | 500 nM and 90 µM |
| Topics | 5-MeO-DMT DMT |
| Keywords | Ventral tegmental area Electrophysiology Membrane potential Bursting Conductance Amphetamine Subthreshold conduction Calcium imaging Patch clamp Endocrinology Premovement neuronal activity |
| Key points | DMT at a high concentration (90 μM) increases action potential firing and alters subthreshold conductance in female, but not male, mouse VTA I_h-negative neurons, while raising cytosolic calcium in both sexes. |
Abstract
ABSTRACT Depression and substance use disorder (SUD) affect millions globally and unfortunately, while established treatments exist, they are not always adequate. Psychedelics have emerged as a promising avenue for development of more effective pharmacological interventions. Dimethyltryptamine (DMT), a classic psychedelic, has shown anti‐depressive and anti‐addictive properties in preclinical studies, observational evaluations, and limited controlled trials; however, the exact mechanism(s) of action(s) are still unknown. In the present ex vivo study, we provide the first evaluation of the electrophysiological effects of acute DMT exposure at two concentrations in male and female I h ‐negative neurons of the mouse ventral tegmental area (VTA). The VTA plays a central role in regulating emotion and motivated behavior, and I h ‐negative neurons, which are putatively inhibitory, shape VTA output to downstream targets. At the lower concentration, DMT (500 nM) did not exert any effect on evaluated electrophysiological properties of female and male VTA I h ‐negative neurons. At the highest concentration (90 μM), DMT elicited a conductance change at subthreshold potentials and an increase in action potential firing; however, these actions were seen only in female VTA. At the higher concentration, DMT increased cytosolic calcium levels in both sexes. In conclusion, DMT has actions in both male and female I h ‐negative VTA neurons, but the alterations in firing and membrane conductance observed in females indicate activation of mechanisms beyond the calcium changes seen in males. Taken together, these findings highlight the importance of translational research to connect the cellular effects of DMT with its potential long‐term therapeutic outcomes in humans, while accounting for variables such as sex and dose‐dependent responses. image
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
Cites 25
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor Molecular Pharmacology December 1, 2001
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
and 20 more in the library