5-HT2A Receptor Knockout Mice Show Sex-Dependent Differences following Acute Noribogaine Administration.
Sofía Villalba, Bruno González, Stephanie Junge, Alejandra Bernardi, Joaquín González, Catherine Fagúndez, Pablo Torterolo, Ignacio Carrera, Francisco J. Urbano, Verónica Bisagno
International Journal of Molecular Sciences January 5, 2024 DOI: 10.3390/ijms25020687 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female 5-HT2A receptor knockout and wild-type mice |
| Intervention | noribogaine |
| Dose | 10 or 40 mg/kg |
| Duration | 30 minutes after injection |
| Topics | Ibogaine Serotonin |
| Keywords | Glutamate receptors Psychedelics Psychedelic effects: noribogaine Psychedelic compound Potent psychedelic Nmda-mediated signaling Varied by sex Ieg Locomotion Brain activity |
| Citations | 9 |
| Key findings | Noribogaine reduces locomotion and NMDA-mediated synaptic currents in the medial prefrontal cortex in a sex- and 5-HT2A receptor-dependent manner in mice. |
Abstract
Noribogaine (noribo) is the primary metabolite from ibogaine, an atypical psychedelic alkaloid isolated from the root bark of the African shrub Tabernanthe iboga. The main objective of this study was to test the hypothesis that molecular, electrophysiological, and behavioral responses of noribo are mediated by the 5-HT2A receptor (5-HT2AR) in mice. In that regard, we used male and female, 5-HT2AR knockout (KO) and wild type (WT) mice injected with a single noribo dose (10 or 40 mg/kg; i.p.). After 30 min., locomotor activity was recorded followed by mRNA measurements by qPCR (immediate early genes; IEG, glutamate receptors, and 5-HT2AR levels) and electrophysiology recordings of layer V pyramidal neurons from the medial prefrontal cortex. Noribo 40 decreased locomotion in male, but not female WT. Sex and genotype differences were observed for IEG and glutamate receptor expression. Expression of 5-HT2AR mRNA increased in the mPFC of WT mice following Noribo 10 (males) or Noribo 40 (females). Patch-clamp recordings showed that Noribo 40 reduced the NMDA-mediated postsynaptic current density in mPFC pyramidal neurons only in male WT mice, but no effects were found for either KO males or females. Our results highlight that noribo produces sexually dimorphic effects while the genetic removal of 5HT2AR blunted noribo-mediated responses to NMDA synaptic transmission.
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
Cited by 10
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models. Nature Communications September 20, 2024
- Ibogaine administration following repeated morphine administration upregulates myelination markers 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin basic protein (MBP) mRNA and protein expression in the internal capsule of Sprague Dawley rats. Frontiers in Neuroscience 2024
- Ibogaine Induces Cardiotoxic Necrosis in Rats-The Role of Redox Processes. International Journal of Molecular Sciences June 13, 2024
- Noribogaine altered intrinsic properties of thalamocortical neurons in a sex-dependent manner Progress in Neuro-Psychopharmacology and Biological Psychiatry August 1, 2025
and 5 more in the library
Cites 37
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- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Single-Dose Psilocybin Treatment for Major Depressive Disorder JAMA August 31, 2023
and 32 more in the library