Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus.
Pharmacology, biochemistry, and behavior – February 01, 1998
Source: PubMed
Summary
Hallucinogens LSD and DOM showed significant effects in Fischer-344 rats, with 63% and 66.4% generalization to ibogaine's stimulus, respectively. This response was blocked by the 5-HT2A antagonist pirenpirone, indicating that serotonin receptors play a role in these effects. Interestingly, ibogaine itself wasn't affected by pirenpirone. Binding assays revealed micromolar affinities for ibogaine (92.5 µM) and harmaline (42.5 µM), suggesting their serotonergic interactions are notable but not crucial for ibogaine's discriminative stimulus effects.
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.