Abstract
The purpose of the present studies was to examine representative uncompetitive 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 discriminate either the uncompetitive, phencyclidine (PCP; 0.32 and 1.0 mg/kg, IM), or the competitive, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylic acid; 1.8 mg/kg, IM), NMDA antagonists from saline. Uncompetitive and competitive NMDA antagonists were examined in generalization 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 antagonists tested were fully generalized to CGS 19755, but not to PCP. The competitive antagonists, however, produced >50% PCP-appropriate responding. The (+) isomer of HA 966 was fully generalized by three of four pigeons discriminating PCP (1.0 mg/kg) or CGS 19755, whereas the racemate and the (−) isomer produced <40% drugappropriate responding in either group. Neither NMDA, morphine, nor pentobarbital produced >10% drug-appropriate responding in either discrimination group. The competitive antagonists tended to produce peak drug-appropriate responding at times greater than 60 min after administration, whereas uncompetitive antagonists produced peak drug-appropriate responding at earlier times. HA 966 also had a relatively slow onset of action as compared to PCP. These results suggest that antagonists acting at different modulatory sites of the NMDA receptor complex produce similar, but not identical, discriminative stimuli.
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Subjects serving in this study were maintained in accordance with guidelines of the Committee on Care and Use of Laboratory Animal Resources, National Research Council [Department of Health, Education and Welfare (National Institutes of Health)] Publication No. 85-23, revised 1985. Portions of these data were presented at the 14th Annual Meeting of the Society for Neuroscience (Baron et al. 1988).
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Baron, S.P., Woods, J.H. Competitive and uncompetitiveN-methyl-d-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine. Psychopharmacology 118, 42–51 (1995). https://doi.org/10.1007/BF02245248
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DOI: https://doi.org/10.1007/BF02245248