There is ample evidence from knock-in mice and from receptor subtype-selective ligands that GABAA receptors containing a2/a3 subunits seem to be of major importance in mediating anxiolysis of diazepam in rodents [1]. Nevertheless, recent evidence indicates that receptors containing al subunits are able to modulate anxiolysis probably mediated by a2/a3 receptors and that the involvement of al receptors depends on the behavioral task investigated [2,3]. In addition, sedation not only seems to be mediated via al receptors but may also be partly dependent on activity mediated by a5 receptors [4]. Thus, the scheme developed from results for knock-in mice has to be modified: al receptors are probably predominantly involved in sedation, anterograde amnesia, and anticonvulsant actions, a2/a3 receptors in anxiolysis, and a5 receptors in learning and memory, but other GABAA receptor subtypes of course could enhance or reduce these effects. Therefore, the relative strength of activation of the various receptor subtypes might be important for the overall behavioral effects of drugs.
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