Further investigations of the serotonergic properties of the ibogaine-induced discriminative stimulus

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 treat ment with the 5-HT2C agonists MK-212 (79.6%) and mCPP (76.4%). This substit ution was completely antagonized by metergoline, an agent with 5-HT2C antag onist properties. However, metergoline was ineffective against ibogaine its elf. This suggests that although ibogaine may act as an agonist at 5-HT2C r eceptors, this interaction is not essential to its discriminative cue. 3. Neither the 5-HT3 agonist, mCPBG (44.3%), nor the 5-HT3 antagonist, onda nsetron (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 substi tute. 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.