Laboratório de Neurofarmacologia e Biofísica, Departamento de Morfologia e Ciências Fisiológicas, Universidade do Estado do Pará - Campus VIII, Marabá, Brazil.
Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Mexico.
Pharmacol Biochem Behav. 2018 Aug;171:66-73. doi: 10.1016/j.pbb.2018.04.007. Epub 2018 Apr 24.
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 GABA receptors has been demonstrated in anamniotes and amniotes alike; however, it 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, Family: Cyprinide) and on a mixed anxiety/panic test on wall lizards (Tropidurus oreadicus, Family: Tropiduridae). 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 anamniotes; B) strengthen the proposal of using anamniote behavior as models in behavioral pharmacology; and C) suggest TSPO/neurosteroidogenesis as a target in treating anxiety disorders.
FGIN-1-27 是 18kDa 转位蛋白（TSPO）的激动剂，TSPO 是一种与神经甾体生成有关的胆固醇转运蛋白。这种蛋白已被确定为苯二氮䓬类药物的外周结合位点；然而，在无羊膜动物中，另一种在羊膜动物中不存在的 TSPO 同工型已被牵连到红细胞生成中。中央苯二氮䓬结合位点的功能保守性在无羊膜动物和羊膜动物中都得到了证明；然而，之前并没有在 TSPO 中得到证明。本研究探讨了 FGIN-1-27 在斑马鱼（Danio rerio，Cyprinide 科）焦虑测试和壁蜥（Tropidurus oreadicus，Tropiduridae 科）混合焦虑/惊恐测试中的行为效应。结果表明，FGIN-1-27 减少了斑马鱼光/暗偏好测试中的焦虑样行为，类似于地西泮，但镇静作用较少。同样，FGIN-1-27 也减少了壁蜥防御测试中的焦虑和恐惧样行为，再次产生的镇静样作用比地西泮少；苯二氮䓬类药物也不能减少该物种的恐惧样行为。这些结果 A）强调了 TSPO 在无羊膜动物防御行为中的功能保守性；B）加强了使用无羊膜动物行为作为行为药理学模型的建议；C）提示 TSPO/神经甾体生成作为治疗焦虑障碍的靶点。
