The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning.

Five groups of rats were given Pavlovian fear conditioning. Four groups were then given extinction training. Prior to extinction these groups received an injection of either the noncompetitive NMDA antagonist MK-801 (0.025, 0.05, or 0.1 mg/kg) or saline. The 5th group received saline but no extinction. During testing, the extinction groups given saline or 0.025 mg/kg of MK-801 showed reduced fear, but the groups that had received the higher doses exhibited as much conditioned fear as the saline group, which had not received extinction. This study showed that MK-801 blocked extinction in a dose-dependent manner. The design of the study ruled out the possibility that the effect was due to state-dependency or to MK-801 interfering with the processing of the conditioned stimulus.