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 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.
Helsley
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S
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, USA. helsley@acsu.buffalo.edu
Rabin
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RA
Winter
J C
JC
D000818:Animals; D004193:Discrimination Learning; D006213:Hallucinogens / Q000494:pharmacology*; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D006213:Hallucinogens; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007050:Ibogaine