Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits.
Soledad Marton, Bruno González, Sebastián Rodríguez-bottero, Ernesto Miquel, Laura Martínez-palma, Mariana Pazos, José Pedro Prieto, Paola Rodríguez, Dalibor Sames, Gustavo Seoane, Cecilia Scorza, Patricia Cassina, Ignacio Carrera
Frontiers in Pharmacology 2019 DOI: 10.3389/fphar.2019.00193 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ibogaine |
| Dose | 20 mg/kg, 40 mg/kg |
| Duration | 3 and 24 hours after administration |
| Topics | Ibogaine |
| Keywords | Bdnf Gdnf Ngf Neurotrophic factors Ibogaine: ibogaine Natural repair proteins Therapeutic effects Pharmacology: ibogaine Impact Mechanism Dose-dependent |
| Citations | 71 |
| Key findings | Ibogaine at 40 mg/kg selectively increased GDNF expression in the ventral tegmental area and substantia nigra, while both doses increased BDNF transcripts in multiple brain regions, suggesting a dose-dependent and region-specific effect on neurotrophic factors. |
Abstract
Ibogaine is an atypical psychedelic alkaloid, which has been subject of research due to its reported ability to attenuate drug-seeking behavior. Recent work has suggested that ibogaine effects on alcohol self-administration in rats are related to the release of Glial cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts the soma of dopaminergic neurons. Although previous reports have shown ibogaine's ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF and other neurotrophic factors (NFs) such as Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct brain regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Rats were i.p. treated with ibogaine 20 mg/kg (I20), 40 mg/kg (I40) or vehicle, and NFs expression was analyzed after 3 and 24 h. At 24 h an increase of the expression of the NFs transcripts was observed in a site and dose dependent manner. Only for I40, GDNF was selectively upregulated in the VTA and SN. Both doses elicited a large increase in the expression of BDNF transcripts in the NAcc, SN and PFC, while in the VTA a significant effect was found only for I40. Finally, NGF mRNA was upregulated in all regions after I40, while I20 showed a selective upregulation in PFC and VTA. Regarding protein levels, an increase of GDNF was observed in the VTA only for I40 but no significant increase for BDNF was found in all the studied areas. Interestingly, an increase of proBDNF was detected in the NAcc for both doses. These results show for the first time a selective increase of GDNF specifically in the VTA for I40 but not for I20 after 24 h of administration, which agrees with the effective dose found in previous self-administration studies in rodents. Further research is needed to understand the contribution of these changes to ibogaine's ability to attenuate drug-seeking behavior.
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 61
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse 2018
- Psychedelic therapy in the treatment of addiction: the past, present and future Frontiers in Psychiatry June 12, 2023
- Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans Chronic Stress August 12, 2020
- Psychedelics therapeutics: What we know, what we think, and what we need to research. Neuropharmacology September 27, 2022
and 56 more in the library
Cites 40
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine Journal of Pharmacology and Experimental Therapeutics 1999
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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. Brain Research September 19, 1994
- 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
and 35 more in the library