Neonatal treatment with a competitive NMDA antagonist results in response-specific disruption of conditioned fear in preweanling rats.

RATIONALE

The N-methyl-D-aspartate (NMDA) receptor has been implicated in processes of neurodevelopment, including cell proliferation, synaptogenesis, and apoptosis. Several studies have reported that administration of NMDA antagonists early in development can cause long-lasting changes in behavior. For example, Gould and Cameron [Behav Neurosci 111:49-56 (1997a)] have shown that a single injection of the competitive NMDA antagonist CGP 43487 on postnatal day (PD) 5 affected behavioral immobility in young rats exposed to the odor of a natural predator.

OBJECTIVES

This experiment was undertaken to determine whether the behavioral effects previously reported would also be seen with conditioned cues. Both stimulus-elicited behavioral immobility (freezing) and changes in heart rate were recorded to examine impairments in responding across multiple measures.

METHODS

Animals were given a single injection of 0, 2.5, or 5.0 mg/kg CGP 43487 on PD 5. On PD 20 subjects were given paired or unpaired presentations of either an olfactory or auditory conditioned stimulus (CS) with a 110-dB-white-noise unconditioned stimulus. CS-elicited freezing and changes in heart rate were measured.

RESULTS

Pups treated with CGP exhibited impairments in conditioned freezing, but were unaffected in their expression of conditioned changes in heart rate, to both olfactory and auditory stimuli.

CONCLUSIONS

These results indicate that neonatal treatment with an NMDA antagonist affects the expression of fear in a response-specific manner. The data suggest that antagonist-induced alterations in neural systems involved in the expression of freezing are affected by NMDA receptor blockade early in life.