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Remarkable selectivity of the in vivo binding of [ 3 H]Ro15‐4513 to α5 subtype of benzodiazepine receptor in the living mouse brain
Author(s) -
Momosaki Sotaro,
Hosoi Rie,
Abe Kohji,
Inoue Osamu
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20812
Subject(s) - in vivo , receptor , chemistry , in vitro , hippocampus , cerebellum , pharmacology , benzodiazepine , medicine , endocrinology , biochemistry , biology , genetics
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.