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 mug) and region-specific manner. Conditioned fear was determined b y the assessment of freezing and the computer-controlled measurement of ina ctivity. Additionally, conditioned heart rate responses were evaluated in t he tone-dependent memory test performed in the home cage with the help of i mplanted ECG transmitters. Injections of APV into the dorsal hippocampus (i .h.) 15 min before training, impaired dose-dependent contextual fear condit ioning without discrimination between contextual foreground (unsignaled sho ck) and background (signaled shock) conditioning as tested 24 h after train ing. Short-term memory analyzed 1 h after training was also impaired. The o bservation that a smaller dose of APV was required for intracerebroventricu lar than for i.h. injection to achieve a similar memory impairment, pointed to the involvement of extrahippocampal NMDA receptors. APV treatment did n ot affect conditioned tone-dependent fear as indicated by unchanged freezin g and heart rate responses of the freely moving mice. The results indicated the contribution of hippocampal and extrahippocamgal NMDA receptors to mul tisensory contextual information processing during acquisition. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.