Discriminative stimulus effects of NMDA in pigeons and monkeys

White Carneaux pigeons (Columba livia) and rhesus monkeys (Macaca mulatta) were trained to discriminate NMDA from saline in a two-response operant procedure. Both species dose dependently generalized NMDA to the training stimulus, although training was difficult and stimulus control was difficult to maintain. The competitive antagonist CGS 19755 (0.32 and 1.0 mg/kg) blocked the discriminative stimulus produced by the training dose of NMDA in pigeons and monkeys. The same doses of CGS 19755 produced rightward, but not dose-dependent, shifts in the NMDA dose-response function in pigeons. The non-competitive NMDA antagonist PCP was unable to block the discriminative stimulus produced by the training dose of NMDA in pigeons. Kainate and AMPA, as well as morphine, pentobarbital and d-amphetamine, engendered ≥ NMDA-appropriate responding in at least 50% of pigeons tested. The finding that compounds from several different classes generalize to the training dose of NMDA suggests that the present discrimination lacks pharmacological selectivity. This discrimination may not serve efficiently as a procedure in which to examine NMDA agonist and/or antagonist activity.