GABA A receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem

Potentiation of GABA A receptor activation through allosteric benzodiazepine (BZ) sites produces the anxiolytic, anticonvulsant and sedative/hypnotic effects of BZs. Using a mouse line lacking α1 subunit expression, we investigated the contribution of the α1 subunit to GABA A receptor pharmacology, function and related behaviors in response to BZ site agonists. Competitive [ 3H]flunitrazepam binding experiments using the Type I BZ site agonist, zolpidem, and the Type I and II BZ site non-specific agonist, diazepam, demonstrated the complete loss of Type I BZ binding sites in α1 −/− mice and a compensatory increase in Type II BZ binding sites (41±6%, P