Impairment of conditioned contextual fear of C57BL/6J mice by intracerebral injections of the NMDA receptor antagonist APV.

The effects of acute injections of the NMDA receptor antagonist APV on one-trial fear conditioning of C57BL/6J mice were investigated in a time, dose (0.4-3.2 microg) and region-specific manner. Conditioned fear was determined by the assessment of freezing and the computer-controlled measurement of inactivity. Additionally, conditioned heart rate responses were evaluated in the tone-dependent memory test performed in the home cage with the help of implanted ECG transmitters. Injections of APV into the dorsal hippocampus (i.h.) 15 min before training, impaired dose-dependent contextual fear conditioning without discrimination between contextual foreground (unsignaled shock) and background (signaled shock) conditioning as tested 24 h after training. Short-term memory analyzed 1 h after training was also impaired. The observation that a smaller dose of APV was required for intracerebroventricular than for i.h. injection to achieve a similar memory impairment, pointed to the involvement of extrahippocampal NMDA receptors. APV treatment did not affect conditioned tone-dependent fear as indicated by unchanged freezing and heart rate responses of the freely moving mice. The results indicated the contribution of hippocampal and extrahippocampal NMDA receptors to multisensory contextual information processing during acquisition.