Joordens R J, Hijzen T H, Peeters B W, Olivier B
Department of Psychopharmacology, Faculty of Pharmacy, Rudolf Magnus Institute of Neurosciences, Utrecht University, The Netherlands.
Psychopharmacology (Berl). 1996 Jul;126(2):104-9. doi: 10.1007/BF02246344.
The fear-potentiated startle response paradigm is used to investigate anxiolytic properties of drugs. The first objective of the present study was to further investigate the predictive validity of this paradigm. The anxiolytics chlordiazepoxide (2.5-10 mg/ kg IP) and oxazepam (1-10 mg/kg PO) and the putative anxiolytic flesinoxan (1-10 mg/kg PO) decreased startle potentiation dose-dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5-20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs attenuate startle potentiation without affecting control startle levels, although some studies report altered control startle amplitudes. The second objective was to investigate whether different effects on control startle amplitudes are related to different startle devices. Therefore, the drugs were tested in two laboratories. Results showed no significant differences between laboratories, indicating that equipment is not a critical factor in the drug-induced alteration of control startle levels. In an additional experiment, it was shown that flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation, supporting the idea that the attenuating effect of flesinoxan on the fear-potentiated startle response is due to its anxiolytic properties. Thus, the fear-potentiated startle response paradigm appears a valid and reliable model for anxiolytic properties of drugs.
恐惧增强惊吓反应范式用于研究药物的抗焦虑特性。本研究的首要目的是进一步探究该范式的预测效度。抗焦虑药物氯氮卓(腹腔注射2.5 - 10毫克/千克)、奥沙西泮(口服1 - 10毫克/千克)以及假定的抗焦虑药物氟辛克生(口服1 - 10毫克/千克)均剂量依赖性地降低惊吓增强,表明具有抗焦虑作用。抗抑郁药物氟伏沙明(口服5 - 20毫克/千克)不影响惊吓增强。理想情况下,抗焦虑药物可减弱惊吓增强而不影响对照惊吓水平,尽管一些研究报告称对照惊吓幅度有所改变。第二个目的是研究对对照惊吓幅度的不同影响是否与不同的惊吓装置有关。因此,在两个实验室对这些药物进行了测试。结果显示实验室之间无显著差异,表明设备并非药物诱导对照惊吓水平改变的关键因素。在一项额外实验中,结果表明氟辛克生(口服10毫克/千克)不影响士的宁诱导的惊吓增强,支持了氟辛克生对恐惧增强惊吓反应的减弱作用归因于其抗焦虑特性这一观点。因此,恐惧增强惊吓反应范式似乎是药物抗焦虑特性的一个有效且可靠的模型。