Role of the NMDA receptor subunit in the expression of the discriminative stimulus effect induced by ketamine.
European journal of pharmacology June 29, 2001 M Narita, K Yoshizawa, M Nomura et al.
Ketamine, an NMDA receptor antagonist used as an anesthetic, can produce psychotomimetic effects like nightmares and hallucinations with chronic use. In Fischer 344 rats trained to discriminate ketamine (5 mg/kg) from saline, non-competitive NMDA receptor antagonists that block NR2A- and NR2B-containing receptors (phencyclidine, dizocilpine) and an NR2A-preferring antagonist (dextromethorphan) fully substituted for the ketamine cue in a dose-dependent manner. The NR2B-selective antagonist ifenprodil, the competitive NMDA antagonist CPP, and the sigma receptor ligand DTG did not generalize. The findings suggest that antagonism of NR1/NR2A-containing NMDA receptors may be critical for producing ketamine's discriminative stimulus effects.