Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus.
Scott Helsley, David Fiorella, R A Rabin, Jerrold C Winter
Pharmacology, biochemistry, and behavior February 1, 1998 DOI: 10.1016/s0091-3057(97)00451-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Fischer-344 rats |
| Interventions | Lysergic acid dimethylamide (LSD) (-)-2 5-dimethoxy-4-methyl-amphetamine (DOM) pirenpirone ibogaine harmaline 12-hydroxyibogamine (noribogaine) N-ethoxycarbonyl-2-ethoxy-1 2-dihydroquinoline (EEDQ) |
| Dose | 10 mg/kg I.P. |
| Duration | 60 min presession |
| Topics | Ibogaine |
| Citations | 35 |
| Key points | Ibogaine's discriminative stimulus effects are not primarily mediated by the 5-HT2A receptor, despite LSD and DOM producing ibogaine-like effects through that receptor. |
Abstract
In the present investigation, the ability of two known hallucinogens, lysergic acid dimethylamide (LSD) and (-)-2,5-dimethoxy-4-methyl-amphetamine (DOM), to substitute for the ibogaine-induced discriminative stimulus (10 mg/kg I.P., 60 min presession) was assessed in Fischer-344 rats. In these subjects, intermediate levels of generalization were observed to both agents (LSD, 63%; DOM, 66.4%). This intermediate generalization was completely blocked by pretreatment with the 5-HT2A antagonist pirenpirone, suggesting that the ibogaine-like effects of these agents are mediated by the 5-HT2A receptor. However, pirenpirone did not antagonize ibogaine itself, nor did it antagonize the ibogaine-like effects of harmaline and 12-hydroxyibogamine (noribogaine). To further evaluate the serotonergic properties of ibogaine, in vivo protection assays and in vitro binding assays were employed. Micromolar 5-HT2A affinity was observed with ibogaine (92.5 microM), 12-hydroxyibogamine (34.5 microM), and harmaline (42.5 microM). Despite the apparently low affinity of these agents, both ibogaine and harmaline, but not 12-hydroxyibogamine, produced significant protection from receptor alkylation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) when given 60 min prior to this alkylating agent. The results of these studies suggest that although ibogaine may produce some of its effects via interactions with 5-HT2A receptors, these do not appear to be essential to the ibogaine-induced discriminative stimulus.