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

Peter P. Roy-Byrne, MD

Published: February 15, 2005

Article Abstract

Benzodiazepines bind to a specific site on the γ-aminobutyric acid (GABA)-benzodiazepine receptorcomplex. This complex has been implicated in the pathophysiology of anxiety by numerous preclinicaland clinical studies. Preclinical studies have shown that there are multiple molecular forms ofthis 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 anxietyresponse in animals and humans. Human studies have shown that patients with pathologic anxietyhave anomalous responses to drugs that specifically bind to these receptors and have reduced numbersof benzodiazepine receptors in key brain areas that regulate anxiety responses. More recent preclinicalstudies suggest that molecular alterations in this receptor complex may produce findings in animalssimilar to those observed in anxious humans. Finally, chronic treatment with benzodiazepines causesthe development of tolerance, which may be associated with molecular changes and a pharmacologicresponse profile similar to that observed in pathologically anxious humans.

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