The psychoactive compound ibogaine sex-dependently alters the firing rate and afterhyperpolarization of Ih-negative neurons in the mouse ventral tegmental area
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen, Uffe Kristiansen, Kristi A. Kohlmeier
Neuroscience October 5, 2025 DOI: 10.1016/j.neuroscience.2025.10.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Putative GABAergic VTA neurons from male and female mice |
| Intervention | Ibogaine |
| Dose | 100 µM |
| Topics | Ibogaine |
| Keywords | Afterhyperpolarization Ventral tegmental area Excitatory postsynaptic potential Gabaergic Bursting Population Rheobase Pars compacta Membrane potential Dopaminergic Inhibitory postsynaptic potential Calbindin Cellular neuroscience Neuropharmacology Neuron Electrophysiology |
| Citations | 1 |
| Key findings | Ibogaine induces sex-dependent changes in VTA neuron activity, decreasing firing rate in males and altering afterhyperpolarization in females, while increasing intracellular calcium in both sexes. |
Abstract
Depression and substance use disorder affect millions world-wide, and risk factors include sex. Conventional pharmacotherapies show at best a 50 % success rate. Psychedelics exhibit both anti-addictive and anti-depressive properties. One of these, ibogaine, a root bark sourced alkaloid, interacts with receptors implicated in anti-depressive and anti-addictive effects with affinities in the micromolar range. However, cellular actions underlying therapeutic properties are not well understood. In this study, for the first time, we evaluated the cellular effects of 100 µM ibogaine on putative GABAergic neurons of the ventral tegmental area (VTA), as activity of neurons in this nucleus, which includes dopamine neurons, modulates emotion and motivated behavior. Neurons from male (n = 14) and female mice (n = 16) were putatively identified as GABAergic based on lack of I h -current. While we detected no ibogaine induced effects on membrane currents, membrane potential, I-V relationship, rheobase or spontaneous excitatory postsynaptic currents (sEPSCs) in either sex, rises in intracellular calcium were induced in males and females. Further, ibogaine decreased the action potential firing rate in males, but not in females, whereas altered afterhyperpolarization kinetics were noted in females, but not males. Interestingly, at baseline, male I h -negative VTA neurons fired action potentials at a significantly higher frequency than females, however, membrane currents, I-V relationship, membrane potential, rheobase, and sEPSCs did not differ between sexes. Our data suggest that sex-based firing differences exist in a subpopulation of VTA neurons and further, ibogaine induces changes in neuronal signaling in this population that differ between males and females, which could contribute to therapeutic actions.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cites 16
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Journal of Neuroscience January 19, 2005
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
and 11 more in the library