NMDA receptors in the pontine brainstem are necessary for fear potentiation of the startle response.

Abstract

The fear-potentiated startle model in rats is a valuable animal test for the investigation of the neural and neurochemical basis of fear. In this model, rats are trained to associate a neutral stimulus with an aversive stimulus, so that after conditioning the conditioned stimulus alone elicits a state of fear leading to an exaggerated acoustic startle response. The fear-potentiated startle model does not require instrumental responding for the indication of states of fear. The acoustic startle response is mediated by a simple brainstem circuit, with the caudal pontine reticular nucleus as an interface that receives input from startle-enhancing circuits. In the present study, we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors on neurones of the caudal pontine reticular nucleus are involved in the mediation of fear-potentiated startle. After fear-conditioning, we injected the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5), into the caudal pontine reticular nucleus of awake rats and tested the effect on the expression of fear-potentiated startle. Injections of AP-5 (0.125-0.5 nmol) into the caudal pontine reticular nucleus dose dependently attenuated fear-potentiated startle without affecting the baseline amplitude of the acoustic startle response. The results suggests that, in the caudal pontine reticular nucleus, glutamate may mediate fear-potentiated startle via NMDA receptors.