Failure of ibogaine to produce phencyclidine-like discriminative stimulus effects in rats and monkeys.

Ibogaine did not produce effects similar to phencyclidine (PCP) in rats or rhesus monkeys trained to discriminate PCP from saline or sham injection. In rats, ibogaine showed no substitution for PCP at doses from 5.6 to 17.6 mg/kg. In monkeys, ibogaine also failed to generalize to PCP at doses from 0.5 to 4.0 mg/kg. Lysergic acid diethylamide (LSD) only partially substituted for PCP in rats and produced little PCP-associated lever pressing in monkeys. These results indicate important behavioral differences between PCP and hallucinogens like LSD and ibogaine and do not support the idea that ibogaine's binding to the PCP site on NMDA receptors drives its acute effects.

Study at a glance

Abstract

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.