Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD.
The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine.
Palumbo
P A
PA
School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Winter
J C
JC
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D005795:Generalization, Stimulus / Q000187:drug effects; D007050:Ibogaine / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D010918:Pizotyline / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012702:Serotonin Antagonists; D013268:Stimulation, Chemical; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D012702:Serotonin Antagonists; D010918:Pizotyline; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D015016:Yohimbine; D007050:Ibogaine; D008238:Lysergic Acid Diethylamide