COMPETITIVE AND UNCOMPETITIVE N-METHYL-D-ASPARTATE ANTAGONIST DISCRIMINATIONS IN PIGEONS - CGS-19755 AND PHENCYCLIDINE

The purpose of the present studies was to examine representative uncom petitive and competitive NMDA antagonists, as well as the glycine/NMDA antagonist, HA 966, in pigeons trained to discriminate either PCP or CGS 19755 from saline. Separate groups of pigeons were trained to disc riminate either the uncompetitive, phencyclidine (PCP; 0.32 and 1.0 mg /kg, IM), or the competitive, CGS 19755 (cis-4-phophonomethyl-2-piperi dine-carboxylic acid; 1.8 mg/kg, IM), NMDA antagonists from saline. Un competitive and competitive NMDA antagonists were examined in generali zation studies, as were the racemate and the (+) and (-) stereoisomers of HA 966 (3-amino-1-hydroxypyrrolid-2-one). Dizocilpine (MK 801) was fully generalized to PCP but not to CGS 19755. All competitive NMDA a ntagonists tested were fully generalized to CGS 19755, but not to PCP. The competitive antagonists, however, produced >50% PCP-appropriate r esponding. The (+) isomer of HA 966 was fully generalized by three of four pigeons discriminating PCP (1.0 mg/kg) or CCS 19755, whereas the racemate and the (-) isomer produced 40% drug-appropriate responding i n either group. Neither NMDA, morphine, nor pentobarbital produced >10 % drug-appropriate responding in either discrimination group. The comp etitive antagonists tended to produce peak drug-appropriate responding at times greater than 60 min after administration, whereas uncompetit ive antagonists produced peak drug-appropriate responding at earlier t imes. HA 966 also had a relatively slow onset of action as compared to PCP. These results suggest that antagonists acting at different modul atory sites of the NMDA receptor complex produce similar, but not iden tical, discriminative stimuli.