Common and uncommon behavioural effects of antagonists for different modulatory sites in the NMDA receptor/channel complex.

The behavioural significance of the N-methyl-D-aspartate (NMDA) receptor/channel complex was investigated in rats, using different types of antagonists including D-2-amino-phosphonovaleric acid, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid, 7-Cl kynurenate, ifenprodil, phencyclidine (PCP), MK-801, ketamine, (+/-)-N-allylnormetazocine, dextromethorphan, ZnCl2, and MgCl2. All antagonists produced an impairment of learning and muscle relaxation when administered i.c.v. Frequent circling was characteristically produced by ligands for PCP binding sites and was unaffected by concomitant administration of a competitive NMDA receptor antagonist. These results suggest that the NMDA receptor/channel plays an important role in regulating learning/memory processes and muscle tone, whereas PCP binding sites unassociated with the NMDA channel are involved in the production of characteristic circling behaviour.