The value of genetic and pharmacological approaches to understanding the complexities of GABAA receptor subtype functions: The anxiolytic effects of benzodiazepines

The identification of γ-aminobutyric acid A (GABAA) receptor subunit genes over the last twenty years has shown that GABAA receptors are made up of many different subtypes. As such the dissection of which receptor subtypes mediate which functions of clinically useful GABAergic drugs, such as benzodiazepines, has been extremely complicated. Two complimentary approaches have been taken: the development of subtype-selective drugs and the genetic manipulation of different receptor subunits. Both have yielded exciting results, but sometimes with contradictory findings. This review highlights the strengths and weaknesses of both approaches, illustrating with specific discussion of the work, to uncover which receptor subtype(s) mediates the anxiolytic effects of benzodiazepines.