Further investigations of the serotonergic properties of the ibogaine-induced discriminative stimulus.
S Helsley, R A Rabin, J C Winter
Progress in neuro-psychopharmacology & biological psychiatry February 1, 1999 DOI: 10.1016/s0278-5846(98)00101-8 (opens in new tab) via PubMed
Summary
AI-generated from the abstractIn rats trained to recognize ibogaine's effects, activating 5-HT2C receptors with MK-212 or mCPP produced ibogaine-like responses (79.6% and 76.4% of the time), and this substitution was blocked by the 5-HT2C antagonist metergoline. However, metergoline did not block ibogaine itself, indicating that while ibogaine may activate 5-HT2C receptors, this action is not necessary for its distinctive cue. Neither a 5-HT3 agonist nor antagonist, nor a 5-HT1A agonist or antagonist, substituted for ibogaine, and a 5-HT1A antagonist did not block ibogaine's effects. Thus, 5-HT1A and 5-HT3 receptors appear uninvolved in ibogaine's discriminative stimulus.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats trained to discriminate ibogaine from water |
| Interventions | MK-212 mCPP metergoline mCPBG ondansetron 8-OH-DPAT WAY-100635 |
| Topics | Ibogaine |
| Keywords | Ibogaine's unique cue Ibogaine's effects Full ibogaine experience Ibogaine's characteristic stimulus Serotonin receptors |
| Citations | 9 |
| Key finding | 5-HT2C receptor activation can mimic ibogaine's cue but is not essential to it, while 5-HT1A and 5-HT3 receptors are not involved in ibogaine's discriminative stimulus. |
Abstract
1. 5-HT3, 5-HT2C, and 5-HT1A receptor ligands were assessed in rats trained to discriminate ibogaine from water. 2. Significant ibogaine-appropriate responding was observed following treatment with the 5-HT2C agonists MK-212 (79.6%) and mCPP (76.4%). This substitution was completely antagonized by metergoline, an agent with 5-HT2C antagonist properties. However, metergoline was ineffective against ibogaine itself. This suggests that although ibogaine may act as an agonist at 5-HT2C receptors, this interaction is not essential to its discriminative cue. 3. Neither the 5-HT3 agonist, mCPBG (44.3%), nor the 5-HT3 antagonist, ondansetron (48.9%) substituted for ibogaine. Likewise, the 5-HT1A agonist 8-OH-DPAT (34.7%) and the 5-HT1A antagonist WAY-100635 (30.1%) failed to substitute. Furthermore, WAY-100635 failed to antagonize the ibogaine cue. 4. Unlike 5-HT2C receptors, 5-HT1A and 5-HT3 receptors do not appear to be involved in the ibogaine stimulus.