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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-aspartate receptor (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) before tone-shock pairings caused a dose-dependent suppression of acquisition of fear of contextual cues associated with shock. Acquisition of fear of the tone was not impaired. Experiment 2 showed that the fear of the tone was associative and that this tone-shock association was less affected by APV than was a context-shock association. Rats receiving 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 weeks) fear memories.