DIFFERENTIAL-EFFECTS OF THE N-METHYL-D-ASPARTATE ANTAGONIST DL-2-AMINO-5-PHOSPHONOVALERATE ON ACQUISITION OF FEAR OF AUDITORY AND CONTEXTUAL CUES

Intracerebroventricular (icv) administration of the N-methyl-D-asparta te receptor (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) bef ore tone-shock pairings caused a dose-dependent suppression of acquisi tion of fear of contextual cues associated with shock. Acquisition of fear of the tone was not impaired. Experiment 2 showed that the fear o f the tone was associative and that this tone-shock association was le ss affected by APV than was a context-shock association. Rats receivin g APV before context-shock pairings showed an equivalent loss of fear regardless of whether testing occurred 1 or 28 days after training. It appears that icv administration of APV blocks acquisition of context conditioning by affecting NMDA receptors in the hippocampus. Activity at these receptors at the time of acquisition seems critical for later expression of both intermediate (1 day to 2 weeks) and remote (4 week s) fear memories.