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The GABA-Benzodiazepine Receptor Complex: Structure, Function, and Role in Anxiety

J Clin Psychiatry 2005;66(suppl 2):14-20

Benzodiazepines bind to a specific site on the γ-aminobutyric acid (GABA)-benzodiazepine receptor complex. This complex has been implicated in the pathophysiology of anxiety by numerous preclinical and clinical studies. Preclinical studies have shown that there are multiple molecular forms of this receptor complex, that these genetically coded variations are linked to specific actions of the benzodiazepines, and that receptors are located in neuroanatomical areas known to mediate the anxiety response in animals and humans. Human studies have shown that patients with pathologic anxiety have anomalous responses to drugs that specifically bind to these receptors and have reduced numbers of benzodiazepine receptors in key brain areas that regulate anxiety responses. More recent preclinical studies suggest that molecular alterations in this receptor complex may produce findings in animals similar to those observed in anxious humans. Finally, chronic treatment with benzodiazepines causes the development of tolerance, which may be associated with molecular changes and a pharmacologic response profile similar to that observed in pathologically anxious humans.