Evaluation of the reinforcing and discriminative stimulus effects of the N-methyl-D-aspartate competitive antagonist NPC 17742 in rhesus monkeys

The phencyclidine (PCP)-like effects of the N-methyl-D-aspartate (NMDA) competitive antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 17742) were evaluated in three behavioral tests in rhesus monkeys. The discriminative stimulus properties of NPC 17742 (2-24 mg/kg, i.m.) were tested in four rhesus monkeys trained to discriminate PCP from saline under a fixed-ratio (FR) 50 schedule of food reinforcement. In three of the monkeys, NPC 17742 showed complete substitution for PCP at doses which did not decrease rates of responding. Intravenous self-administration of NPC 17742 (50-800 micrograms/kg/infusion) was tested under a FR schedule of reinforcement in four monkeys trained to lever press for infusions of PCP. At least one dose of NPC 17742 functioned as a reinforcer in two of the monkeys. A second self-administration study, employing a 10 min fixed interval schedule of reinforcement, was performed in three monkeys trained to self-administer PCP during three daily sessions. Compared with PCP, NPC 17742 (0.4-1.6 mg/kg/infusion) maintained very low rates of responding; NPC 17742 could not be clearly established as a reinforcer in this procedure. The data show that NPC 17742 has some PCP-like behavioral effects, and may function as a weak reinforcer in some subjects under specific conditions. The results provide further evidence that both similarities and differences exist between the behavioral effects of PCP and competitive NMDA antagonists.