A microPET comparison of the effects of etifoxine and diazepam on [C-11]flumazenil uptake in rat brains

作者：Bouillot Caroline; Bonnefoi Frederic; Liger Francois; Zimmer Luc^*

来源：Neuroscience Letters, 2016, 612: 74-79.

DOI：10.1016/j.neulet.2015.11.042

• Rodent
• Anxiolytic drug
• GABA
• Allosteric site

Using positron emission tomography (PET), the present study assessed the binding of [C-11]flumazenil to GABA-A receptors in anesthetized rats following a single intravenous injection of an active dose of either etifoxine (25 mg/kg) or diazepam (1 mg/kg), which are both anxiolytic drugs. ([)1(1)C]flumazenil binding was measured in five discrete brain structures, namely the caudate putamen, hippocampus, cerebellum, occipital cortex and parietal cortex. As expected, diazepam injection produced a significant decrease in [11C]flumazenil binding, which was interpreted as benzodiazepine GABA-A receptor occupancy, whereas etifoxine increased the binding of [C-11]flumazenil. This first use of in vivo imaging after etifoxine administration revealed the activated binding pattern of [C-11]flumazenil and highlighted the pharmacological differences between etifoxine and benzodiazepines. Using the same [C-11] flumazenil radiotracer, PET neuroimaging could be applied to larger animals and, ultimately, to human subjects, thus providing new perspectives for better defining the molecular pharmacology of etifoxine.

• 出版日期2016-1-26