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Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310, USA.
The discriminative stimulus properties of ibogaine were investigated in rats trained to discriminate phencyclidine (PCP; 2.0 mg/kg, I.P.) from saline under a two-lever fixed-ratio (FR) 32 schedule of food reinforcement. Ibogaine (5.6-17.6 mg/kg, I.P.) showed a complete lack of substitution. Ibogaine (0.5-4.0 mg/kg, I.M.) also failed to generalize in rhesus monkeys trained to discriminate PCP (0.1 mg/kg, I.M.) from sham injection. Lysergic acid diethylamide (LSD), tested as a reference compound, produced partial substitution for PCP in rats and occasioned little responding on the PCP-associated lever in monkeys. These results demonstrate important differences between the behavioral effects of PCP and other types of hallucinogenic drugs such as LSD and ibogaine and do not support the hypothesis that the affinity of ibogaine for the PCP site on N-methyl-D-aspartate (NMDA) receptors plays a major role in its acute behavioral effects.
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