Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research.
Jonathan Cachat, Evan J. Kyzar, Christopher Collins, Siddharth Gaikwad, Jeremy Green, Andrew Roth, Mohamed El-Ounsi, Ari Davis, Mimi Pham, Samuel Landsman, Adam Michael Stewart, Allan V. Kalueff
Behavioural Brain Research 2013 DOI: 10.1016/j.bbr.2012.08.041 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult zebrafish (Danio rerio) |
| Intervention | Ibogaine |
| Dose | 10 and 20 mg/L |
| Topics | Ibogaine |
| Keywords | Zebrafish model Zebrafish research Animal model Aquatic model Research model Biological model *in vivo* model Experimental model Ibogaine effects Hallucinogen effects Psychoactive drug effects Psychedelic effects Drug profiles Substance effects Behavioral pharmacology Psychopharmacology Drug-induced changes Animal behavior Zebrafish behavior Behavioral changes Ethology Neurobehavioral studies Spatial exploration Social behavior Dive reflex Mirror interaction Locomotion Activity Drug screening High-throughput screening Preclinical research Drug discovery Pharmaceutical screening Screening assays Drug development |
| Citations | 112 |
| Key findings | Ibogaine dose-dependently reversed the diving response, reduced dark preference, altered spatial exploration, promoted mirror exploration, disrupted shoaling cohesion, and induced melanophore aggregation without changing brain c-fos or cortisol levels. |
Abstract
An indole alkaloid, ibogaine is the principal psychoactive component of the iboga plant, used by indigenous peoples in West Africa for centuries. Modulating multiple neurotransmitter systems, the drug is a potent hallucinogen in humans, although its psychotropic effects remain poorly understood. Expanding the range of model species is an important strategy for translational neuroscience research. Here we exposed adult zebrafish (Danio rerio) to 10 and 20mg/L of ibogaine, testing them in the novel tank, light-dark box, open field, mirror stimulation, social preference and shoaling tests. In the novel tank test, the zebrafish natural diving response (geotaxis) was reversed by ibogaine, inducing initial top swimming followed by bottom dwelling. Ibogaine also attenuated the innate preference for dark environments (scototaxis) in the light-dark box test. While it did not exert overt locomotor or thigmotaxic responses in the open field test, the drug altered spatiotemporal exploration of novel environment, inducing clear preference of some areas over others. Ibogaine also promoted 'mirror' exploration in the mirror stimulation test, disrupted group cohesion in the shoaling test, and evoked strong coloration responses due to melanophore aggregation, but did not alter brain c-fos expression or whole-body cortisol levels. Overall, our results support the complex pharmacological profile of ibogaine and its high sensitivity in zebrafish models, dose-dependently affecting multiple behavioral domains. While future investigations in zebrafish may help elucidate the mechanisms underlying these unique behavioral effects, our study strongly supports the developing utility of aquatic models in hallucinogenic drug research. High sensitivity of three-dimensional phenotyping approaches applied here to behavioral effects of ibogaine in zebrafish provides further evidence of how 3D reconstructions of zebrafish swimming paths may be useful for high-throughput pharmacological screening.
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 15
- The Iboga Alkaloids. Progress in the chemistry of organic natural products 2017
- Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models Zebrafish March 22, 2016
- Anxiolytic-like effects of noribogaine in zebrafish. Behavioural Brain Research July 14, 2017
- Acute behavioral and Neurochemical Effects of Novel N -Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish ACS Chemical Neuroscience June 7, 2022
- The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish Frontiers in Psychiatry August 13, 2017
and 10 more in the library
Cites 35
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Psychedelics and the Human Receptorome PLoS One 2010
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- 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
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
and 30 more in the library