In Vivo Ibogaine Blockade and In Vitro PKC Action of Cocainea.
Emmanuel S Onaivi, Syed F. Ali, Amitabha Chakrabarti
Annals of the New York Academy of Sciences May 1, 1998 DOI: 10.1111/j.1749-6632.1998.tb08238.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice and PC 12 cells |
| Interventions | Ibogaine Cocaine |
| Dose | 1-5.0 mg/kg ibogaine; 1.0 mg/kg cocaine; 2.5 mg/kg ibogaine |
| Duration | 14-day treatment period |
| Topics | Ibogaine |
| Citations | 13 |
| Key points | Ibogaine reversed withdrawal aversions in mice abruptly withdrawn from cocaine and altered anxiety-related behavior, while in PC 12 cells cocaine disrupted PKC isoform expression and activity and calcium levels. |
Abstract
Ibogaine may have antiaddiction potential against alcohol, psychostimulant and opiate abuse, but its mechanism of action is unclear. Ibogaine, however, has been demonstrated in numerous studies to have effects in multiple central nervous system (CNS) neurotransmitters systems. We are using in vitro and in vivo systems to study the effects of cocaine and whether these effects can be blocked by ibogaine. For the In Vivo studies, we first determined the acute and subacute effects of ibogaine (1-5.0 mg/kg) in mice using the plus-maze test. Acutely increasing doses of ibogaine produced a reduced aversion to the open arms. The subacute administration provoked a variable response which was characterized by fluctuations in aversive and antiaversive behavior of the animals to the open arms of the plus-maze during the 14-day treatment period. A separate group of mice received 1.0 mg/kg cocaine for 14 days, and upon abrupt cessation from cocaine treatment, ibogaine 2.5 mg/kg was administered to a subgroup of these mice. Ibogaine reversed the withdrawal aversions produced by the abrupt cessation from cocaine administration. For the in vitro studies, the expression and activity of protein kinase C (PKC) isoforms and Ca2+ levels were examined following the incubation of PC 12 cells with cocaine. This is because PKC plays a key role in a number of cellular and neuronal functions. We report that cocaine disrupts signal transduction in PC 12 cells by altering the expression and activity of PKC isoforms and Ca2+ levels. The data obtained suggest (1) that the PC 12 cells may be useful in studying the neurobiology of abused drugs, like cocaine in vitro, (2) that if anxiety is a factor in drug dependency, then the antiaddictive property of ibogaine In Vivo may be associated with modifying the CNS neurotransmission that may be involved in anxiety. It remains to be determined whether the signaling involving PKC is important in the antiaddictive properties of ibogaine.
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 5
- Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research. Behavioural Brain Research 2013
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation. Annals of the New York Academy of Sciences June 1, 2002
- Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite CNS Drug Reviews September 1, 2000
- Acute ibogaine injection induces expression of the immediate early genes, egr-1 and c-fos, in mouse brain. Brain research. Molecular brain research December 10, 1999
Cites 12
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior November 1, 1995
- Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology May 1, 1992
and 7 more in the library