N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats.

Abstract

Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-Daspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats.In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear.In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear.This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats.In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA.These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats.The association of stimuli and their aversive consequences is a ubiquitous form of learning with obvious adaptive value.One model system for studying the neural substrates underlying aversive learning is Pavlovian fear conditioning in rats.In Pavlovian fear conditioning, an initially neutral stimulus (conditional stimulus, or CS), such as a tone or context, comes to elicit a conditional fear response, such as somatomotor immobility (i.e., freezing), after being paired with an aversive unconditional stimulus (US), such as an electric footshock.In recent years, the understanding of the neural substrates of aversive learning has grown abundantly, and considerable data indicate that the nuclei of the amygdala are essential (for reviews, see Davis, 1992;LeDoux, 1995; Maren & Fanselow, 1996).For instance, destruction of neurons intrinsic to the basolateral amygdala (BLA) produces severe deficits in both the acquisition and the expression of conditional fear (