Role of the amygdala in fear extinction measured with potentiated startle.

Although much is now known about the neural basis of excitatory fear conditioning, much less is known about the neural basis of inhibitory conditioning. One type of inhibitory conditioning is extinction, a process in which stimuli that elicit fear by virtue of previous associations with aversive stimuli such as shock (excitatory fear conditioning) are now presented in the absence of the aversive stimuli (extinction training). As a result, the ability of the conditioned stimulus to elicit fear gradually diminishes. Extinction is different from forgetting and does not reflect an erasure of the original fear memory. Instead, extinction is an active form of inhibitory learning that competes with excitatory fear conditioning. Infusions into the amygdala (a brain area essential for excitatory fear conditioning) of either NMDA receptor antagonists or inhibitors of the NMDA-receptor-linked mitogen-activated protein kinase cascade block extinction learning. Conversely, the NMDA receptor agonist D-cycloserine facilitates extinction after either systemic administration or intra-amygdala infusion. Because therapeutic interventions based on extinction procedures are commonly used to treat fear disorders, and because D-cycloserine is a widely available and safe compound, D-cycloserine or similar agents might be usefully combined with traditional extinction-based approaches in the treatment of clinical fear.