FGIN-1-27, an agonist at translocator protein 18 kDa (TSPO), produces anti-anxiety and anti-panic effects in non-mammalian models

FGIN-1-27 is an agonist at the translocator protein 18 kDa (TSPO), a cholesterol transporter that is associated with neurosteroidogenesis. This protein has been identified as a peripheral binding site for benzodiazepines; in anamniotes, however, a second TSPO isoform that is absent in amniotes has been implicated in erythropoiesis. Functional conservation of the central benzodiazepine binding site located in the GABAA receptors has been demonstrated in anamniotes and amniotes alike; however, the same was not previously demonstrated for TSPO. The present investigation explored the behavioral effects of FGIN-1-27 on an anxiety test in zebrafish (Danio rerio) and on a mixed anxiety/panic test on wall lizaeds (Tropidurus oreadicus). Results showed that FGIN-1-27 reduced anxiety-like behavior in the zebrafish light/dark preference test similar to diazepam, but with fewer sedative effects. Similarly, FGIN-1-27 also reduced anxiety- and fear-like behaviors in the defense test battery in wall lizards, again producing fewer sedative-like effects than diazepam; the benzodiazepine was also unable to reduce fear-like behaviors in this species. These results A) underline the functional conservation of TSPO in defensive behavior in anamniote...Continue Reading