Noribogaine altered intrinsic properties of thalamocortical neurons in a sex-dependent manner
Sofía Villalba, Sofia Bosch, Lucia di Constanzo, Bruno González, Pablo Torterolo, Ignacio Carrera, Francisco J. Urbano, Verónica Bisagno
Progress in Neuro-Psychopharmacology and Biological Psychiatry August 1, 2025 DOI: 10.1016/j.pnpbp.2025.111467 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female 5-HT2AR knockout and wild type mice |
| Intervention | Noribogaine |
| Dose | 10 or 40 mg/kg; i.p. (for gene expression); 50 μM (bath application for patch-clamp) |
| Topics | Ibogaine |
| Keywords | Endocrinology Voltage-dependent calcium channel Gene expression Wild type Genetics |
| Citations | 1 |
| Key findings | Noribogaine's effects on thalamic calcium channel gene expression and current density are sex- and 5-HT2A receptor-dependent. |
Abstract
Noribogaine (Noribo) is the primary metabolite from ibogaine, an atypical psychedelic. The main objective of this study was to evaluate the effect of Noribo on thalamic physiology of calcium channels voltage activation and gene expression and the potential involvement of the 5-HT2A receptor on those effects. Thus, 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.) and measured thalamic mRNA expression of T-type and P/Q-type calcium channels, as well as HCN2. For CACNA1g (T- type) we found that Noribo 10 increased gene expression of this channel; however, this effect was observed only in WT males and KO females. This result suggests that the effect of Noribo 10 on gene expression is both receptor- and sex-dependent. For CACNA1a (P/Q type), we found that Noribo 10 increased the mRNA expression in both sexes. For HCN2, we found that Noribo 10 decreased the mRNA expression in WT and KO females but only in KO males. We also investigated calcium channel current density by patch-clamp recordings of thalamocortical ventrobasal neurons after bath application of Noribo (50 μM) in slices obtained from WT and KO 5-HT2AR mice, male and female. We found that bath-applied Noribo blocked T-type calcium current density only in KO females but not in WT. However, in males no blocking effect of Noribo was observed for both genotypes. Also, calcium current density values appeared to be drastically increased in ventrobasal neurons from female mice, another indication of sex-dependent differences.
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 30
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations Acta Psychiatrica Scandinavica September 21, 2017
- Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia The International Journal of Neuropsychopharmacology April 19, 2015
and 25 more in the library