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      Behavioral and Biochemical Evidence for a Nonessential 5-HT2A Component of the Ibogaine-Induced Discriminative Stimulus

      Pharmacology Biochemistry and Behavior
      Elsevier BV

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          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.

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          Author and article information

          Journal
          Pharmacology Biochemistry and Behavior
          Elsevier BV
          00913057
          February 1998
          : 59
          : 2
          : 419-425
          Article
          10.1016/S0091-3057(97)00451-6
          9476990
          eb032f7f-4b0c-4b8e-99c8-73811ae45791
          © 1998

          https://www.elsevier.com/tdm/userlicense/1.0/

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