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

Sotaro Momosaki, Rie Hosoi, Kohji Abe, Osamu Inoue

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To evaluate the binding characteristics of [3H]Ro15-4513 with the central benzodiazepine (BZ) receptor, inhibition experiments of [3H]Ro15-1788 and [3H]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 [3H]Ro15-1788 and [3H]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 [3H]Ro15-1788 and [3H]Ro15-4513 in all the aforementioned brain regions in vitro. However, in vivo, β-CCE inhibited the binding of [3H]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 [3H]Ro15-1788 was inhibited by 1 mg/kg of β-CCE in all regions. The time-activity curve of [3H]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 [3H]Ro15-4513 with the BZ receptor differed markedly between the in vitro and in vivo condition, and the selectivity of [3H]Ro15-4513 binding to α5 subtype of BZ receptor in the mouse brain seemed to be remarkable under the in vivo condition.

Original languageEnglish
Pages (from-to)928-936
Number of pages9
JournalSynapse
Volume64
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • GABA/BZ receptor
  • In vivo
  • Ro15-4513
  • α5 subtype
  • β-CCE

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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