N-METHYL-D-ASPARTATE (NMDA) AND HA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPRIONATE (AMPA) GLUTAMATE-RECEPTOR ANTAGONISTS HAVE DIFFERENT INTERACTIONS WITH THE DISCRIMINATIVE STIMULI OF ABUSED DRUGS

The effects of the AMPA-receptor antagonists NBQX and GYKI 52466 were compared with those of the NMDA-receptor channel blocker dizocilpine i n two drug discrimination tests. In the first, rats were trained to di scriminate morphine (2 mg/kg) from saline and in the second, to discri minate ketamine (7 mg/kg) from saline, using a two-lever food reinforc ed method. NBQX (1-6 mg/kg) did not substitute for either morphine or ketamine, even at a dose which reduced response rates (6 mg/kg). Likew ise, the non-competitive antagonist GYKI 52466 (5 and 10 mg/kg) produc ed only saline lever responding in the ketamine trained rats. When tes ted in combination with the training drug, NBQX (4.5 mg/kg) did not al ter the morphine generalisation gradient, and similarly, neither NBQX (3 mg/kg) nor GYKI 52466 (5 and 10 mg/kg) interacted with the ketamine cue. In contrast, dizocilpine (0.05 mg/kg) significantly disrupted di scrimination of morphine and produced clear drug lever responding (0.0 125-0.1 mg/kg) in ketamine trained rats. These results suggest that AM PA-receptor antagonists and non-competitive NMDA-antagonists have diff erent stimulus properties.