Remarkable selectivity of the in vivo binding of [ 3 H]Ro15‐4513 to α5 subtype of benzodiazepine receptor in the living mouse brain

To evaluate the binding characteristics of [ 3 H]Ro15‐4513 with the central benzodiazepine (BZ) receptor, inhibition experiments of [ 3 H]Ro15‐1788 and [ 3 H]Ro15‐4513 were performed both in vitro and in vivo, using two BZ ligands, flunitrazepam (FNP), and ethyl‐β‐carboline‐3‐carboxylate (β‐CCE). FNP inhibited the binding of [ 3 H]Ro15‐1788 and [ 3 H]Ro15‐4513 in a dose‐dependent manner in the mouse cerebral cortex, hippocampus, and cerebellum, both in vitro and in vivo. β‐CCE also inhibited the binding of [ 3 H]Ro15‐1788 and [ 3 H]Ro15‐4513 in all the aforementioned brain regions in vitro. However, in vivo, β‐CCE inhibited the binding of [ 3 H]Ro15‐4513 in the cerebral cortex and cerebellum, but not in the hippocampus, even at an injected dose of up to 1mg/kg. In contrast, more than 50% of the in vivo binding of [ 3 H]Ro15‐1788 was inhibited by 1 mg/kg of β‐CCE in all regions. The time‐activity curve of [ 3 H]Ro15‐4513 in the hippocampus also showed no alteration of the peak uptake between the control group and 0.3 mg/kg of β‐CCE coinjected group. These results indicated that the binding characteristics of [ 3 H]Ro15‐4513 with the BZ receptor differed markedly between the in vitro and in vivo condition, and the selectivity of [ 3 H]Ro15‐4513 binding to α5 subtype of BZ receptor in the mouse brain seemed to be remarkable under the in vivo condition. Synapse 64:928–936, 2010. © 2010 Wiley‐Liss, Inc.