Effect of ibogaine on cocaine-induced efflux of [3H] dopamine and [3H] serotonin from mouse striatum.
Henry Sershen, Audrey Hashim, Ábel Lajtha
Pharmacology, Biochemistry, and Behavior April 1, 1996 DOI: 10.1016/0091-3057(95)02098-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro and in vivo experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ibogaine Cocaine CGS-12066A U-62066 |
| Dose | 40 mg/kg or 2 times 40 mg/kg (ibogaine); 10(-6) M (cocaine, CGS-12066A, U-62066 in vitro); 1 mg/kg (CGS-12066A, U-62066 SC); 25 mg/kg (cocaine SC) |
| Duration | Mice killed 2 or 18 h after ibogaine treatment |
| Topics | Ibogaine Serotonin |
| Citations | 21 |
| Key findings | Ibogaine blocks cocaine-induced serotonin efflux in mouse striatal tissue and alters kappa-opioid modulation of serotonin transmission. |
Abstract
Ibogaine, an indole alkaloid with proposed antiaddictive properties, has structural similarity to serotonin and has been shown to have affinity to the kappa-opioid binding site. In addition to the dopamine system, the serotonin system is a major target for cocaine action and the opioid system can affect the serotonin system. Therefore, the present study examined the effect of ibogaine on cocaine-induced, electrically evoked efflux of [3H]dopamine and [3H]serotonin from striatal tissue incubated in vitro, and their modulation by the kappa-opioid system. Cocaine (10(-6) M) added in vitro increased tthe fractional efflux of both [3H]dopamine (FRS2/FRS1 = 2.42 +/- 0.36) and [3H]serotonin (FRS2/FRS1 = 1.31 +/- 0.06). Mice treated in vivo with ibogaine (40 mg/kg or 2 times 40 mg/kg, IP) and killed 2 or 18 h later still showed the cocaine-induced increase in [3H]dopamine, but [3H]serotonin efflux was not increased. The 5-HTIB agonist CGS-12066A (10(-6) M, added in vitro) increased [3H]dopamine release, but did not alter cocaine-induced efflux of [3H]dopamine. CGS-12066A did not affect [3H]serotonin release, but the cocaine-induced increase in [3H]serotonin was inhibited. CGS-12066A (1 mg/kg, SC) potentiated cocaine (25 mg/kg, SC)-induced locomotor activity. Ibogaine pretreatment reduced both the cocaine and the CGS-12066A cocaine-induced increase in locomotor activity. The kappa-opioid agonist U-62066 (10(-6) M, added in vitro) reduced both [3H] dopamine and [3H]serotonin release. This inhibitory effect was blocked by in vivo administration ibogaine. U-62066 did not alter cocaine-induced [3H]dopamine efflux, but reduced cocaine-induced [3H]serotonin efflux. In striatal tissue from ibogaine-pretreated mice, U-62066 restored the cocaine-induced increase in [3H]serotonin release. U-62066 (1 mg/kg, SC) potentiated cocaine-induced behavior and maintained an increased locomotor activity after ibogaine treatment. The results suggest that ibogaine may block the cocainemediated effects on serotonergic transmission, that subsequently modulate dopamine release. The kappa-opioid modulation of serotonergic transmission is also involved.
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 7
- Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment. Pharmacology, Biochemistry, and Behavior June 1, 2003
- Ibogaine and cocaine abuse: pharmacological interactions at dopamine and serotonin receptors. Brain Research Bulletin 1997
- Responses of the extrapyramidal and limbic substance P systems to ibogaine and cocaine treatments. European Journal of Pharmacology February 25, 2000
- The effect of ibogaine on Sigma- and NMDA-receptor-mediated release of [3H]dopamine. Brain Research Bulletin 1996
- Differential responses by neurotensin systems in extrapyramidal and limbic structures to ibogaine and cocaine. Brain Research February 6, 1999
and 2 more in the library
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
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
- The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex. Psychopharmacology May 1, 1994
- Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats. Brain Research March 13, 1992
and 7 more in the library