Viviane Labrie, John C. Roder
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
University of Toronto, Toronto, Ontario, Canada
Neurobiology of Post-traumatic Stress Disorder. Hauppauge, New York: Nova Science Publishers, 2010, 376 pages.

Aberrant glutamatergic transmission has been implicated in the pathophysiology of anxiety disorders. Alterations in NMDA receptor (NMDAR) expression, function, and binding are induced in animal models of fear and stress. NMDARs have a central role in mediating the acquisition and extinction of learned fear responses. Consequently, this has led to investigations examining the therapeutic utility of compounds targeting the NMDAR for the treatment of anxiety syndromes. High-affinity open channel blockers of the NMDAR promote anxiolytic effect in preclinical rodent studies; however the psychotomimetic effects induced by these antagonists have hampered their applicability in clinical settings. Instead, low-affinity NMDAR inhibitors and agonists of the NMDAR glycine binding site have demonstrated therapeutic potential without significant adverse effects. Furthermore, NMDAR glycine site activators have been shown to be effective in accelerating fear extinction in animal studies, and recent clinical trials have supported their efficacy in enhancing exposure therapy in patient with anxiety syndromes. Thus, an improved understanding of the molecular mechanisms underlying stress, fear, and extinction has led to the discovery of highly promising treatment interventions involving the NMDAR.