Using Pavlovian conditioning procedures, combined with measures such as freezing, or the fear-potentiated startle response, considerable progress has been made in the last decade in understanding the biological basis of fear conditioning. Glutamate receptor activation in the amygdala is critical for the acquisition and expression of conditioned fear using auditory or visual conditioned stimuli (CSs). At present, less is known about the biological mechanisms underlying the inhibition of fear, which may be important in the etiology and treatment of anxiety disorders. This proposal will investigate the neural substrates of a form of fear inhibition under tight stimulus control: Pavlovian conditioned inhibition. Conditioned inhibition will be measured as the extent to which the fear-potentiated startle response is reduced by a stimulus trained as a Pavlovian conditioned inhibitor. The role of glutamate transmission in the amygdala in the acquisition and expression of conditioned inhibition will be assessed by local infusion into the amygdala of selective N-methyl-D-aspartate (NMDA) and non-NMDA glutamate antagonists. The results of these studies promise to provide a basis for understanding the way in which a state of fear is gated by stimuli signaling safety.
