Characterization of the discriminable stimulus produced by 2-BFI: effects of imidazoline I(2)-site ligands, MAOIs, beta-carbolines, agmatine and ibogaine.
Nicholas Macinnes, Sheila L. Handley
British Journal of Pharmacology March 1, 2002 DOI: 10.1038/sj.bjp.0704579 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study Peer reviewed |
|---|---|
| Population | Male Hooded Lister rats |
| Interventions | 2-BFI BU216 BU224 BU226 LSL60101 moclobemide RO41-1049 harmane norharmane harmaline ibogaine agmatine LSL60125 lazabemide RO16-1649 SKF10 047 amiloride deprenyl clorgyline |
| Dose | 7 mg kg(-1) i.p. |
| Topics | Ibogaine |
| Keywords | I2 sites Neurochemistry Drug effects |
| Citations | 30 |
| Key points | Imidazoline I2-site ligands produce a discriminable stimulus associated with reversible inhibition of MAO-A, and ibogaine substitutes for this stimulus. |
Abstract
1. The molecular nature and functions of the I(2) subtype of imidazoline binding sites are unknown but evidence suggests an association with monoamine oxidase (MAO). Rats can distinguish the selective imidazoline I(2)-site ligand 2-BFI from vehicle in drug discrimination, indicating functional consequences of occupation of these sites. We have used drug discrimination to investigate the nature of the discriminable stimulus, especially in relation to MAO inhibition. 2. Following training to distinguish 2-BFI 7 mg kg(-1) i.p. from saline vehicle in two-lever operant-chambers, male Hooded Lister rats underwent sessions where test substances were given instead and the proportion of lever presses on the 2-BFI-associated lever (substitution) recorded. 3. 2-BFI; its cogeners BU216, BU224, BU226 and LSL60101; the reversible MAO-A inhibitors moclobemide and RO41-1049; the beta-carbolines harmane, norharmane and harmaline which also reversibly inhibit MAO-A, and the anti-addictive substance ibogaine exhibited potent, dose-dependent substitution for 2-BFI. 4. Agmatine, and LSL60125 substituted at one dose only. The reversible MAO-B inhibitors lazabemide and RO16-1649; the sigma(2)-site ligand SKF10,047 and the I(2A)-site ligand, amiloride, failed to substitute. The irreversible inhibitor of MAO, deprenyl, substituted for 2-BFI while clorgyline did not. 5. These results suggest imidazoline I(2) site ligands produce a common discriminable stimulus that appears associated with reversible inhibition of MAO-A rather than MAO-B, possibly through increases in extracellular concentration of one or more monoamines. Ibogaine exhibits a commonality in its subjective effects with those of I(2)-site ligands.
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 8
- Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. European Journal of Pharmacology June 6, 1995
- The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine. Behavioural Brain Research November 16, 1994
- Acute iboga alkaloid effects on extracellular serotonin (5-HT) levels in nucleus accumbens and striatum in rats. Brain Research August 3, 1998
- Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus. Pharmacology, Biochemistry, and Behavior February 1, 1998
- Ibogaine acts at the nicotinic acetylcholine receptor to inhibit catecholamine release. Brain Research June 22, 1998
and 3 more in the library