Both amygdala- and hippocampus-dependent fear conditioning in animals have been related to long-term potentiation and other forms of synaptic plasticity. Accordingly, blockade of NMDA (N-methyl-D-aspartate) glutamate receptors in the amygdala blocks cue-associated fear conditioning, and NMDA receptor blockade in the hippocampus blocks context-dependent fear conditioning85. Consistent with the notion that extinction represents the formation of a new memory rather than the erasure of an existing memory, administration of D-cycloserine, an NMDA receptor partial agonist, can enhance extinction of fear conditioning in animal models and in patients with PTSD undergoing prolonged exposure therapy86. Blockade of β-adrenergic receptors in the amygdala can also block cue-dependent fear conditioning, and β-adrenergic antagonists have been tested in patients exposed to trauma, with mixed results32,87. In addition, fear conditioning and its extinction are regulated by activation of GRs in the hippocampus and perhaps in the amygdala, which suggests the possible use of glucocorticoids in the treatment of trauma88. However, whether β-adrenergic and GR levels or functioning are different in resilient and non-resilient individuals has not yet been studied.
