The discriminative stimulus effects of MK-801: Generalization to other N-methyl-D-aspartate receptor antagonists

Rats were trained to discriminate a dose of the NMDA antagonist MK-801 from saline using a standard, two-lever, operant procedure. The acquisition of this discrimination was rapid, rats reaching criterion performance in a mean of 32 sessions. The discriminative stimulus produced by MK-801 generalized to phencyclidine and (+)N-allylnormetazocine but only low levels of generalization were seen with (-)N-allylnormetazocine and with the anti- ischaemic drug ifenprodil and its derivative SL 82.0715. The MK-801 stimulus was partially antagonized by haloperidol. The results show that MK-801 can produce a discriminative stimulus which is shared by other non-competitive NMDA antagonists which have similar behavioural effects in other procedures. However, ifenprodil and SL 82.0715, which have also been shown to antagonize the effects of NMDA, do not produce similar behavioural effects or discriminative stimuli presumably because they act through a different site.