The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor.
Using a two-lever operant drug discrimination paradigm, rats have been trained to discriminate between the administration of saline and R-(+)-HA-966 (R-(+)-3-amino-1-hydroxypyrrolid-2-one, 30 mg/kg i.p.) an antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex. Drug-appropriate responding was not induced in stimulus generalisation experiments when the non-competitive NMDA receptor antagonist, phencyclidine (PCP, 1-8 mg/kg i.p.) was substituted for (+)-HA-966. Similarly, (+)-HA-966 (6-50 mg/kg i.p.) did not induce drug-appropriate responding in animals trained to discriminate PCP (3 mg/kg i.p.) from saline. The results suggest that the behavioural profile of compounds attenuating the actions of NMDA via blockade of the glycine modulatory site may be substantially different from those acting at the ion channel of the NMDA receptor complex.
Singh
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L
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Menzies
R
R
Tricklebank
M D
MD
D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D010622:Phencyclidine