Winslow James T, Noble Pamela L, Davis Michael
Yerkes National Primate Research Center, Psychiatry and Behavioral Science, Center for Behavioral Neuroscience, Emory University, Atlanta, Georgia, USA.
Biol Psychiatry. 2007 Feb 1;61(3):389-95. doi: 10.1016/j.biopsych.2006.03.012. Epub 2006 May 30.
Modulation of the acoustic startle response by aversive sensory stimulation is a simple and objective indicator of emotionality in rodents and human beings that has been extremely valuable for the analysis of neural systems associated with fear and anxiety. We have described a paradigm for measuring fear-potentiated, whole-body acoustic startle in nonhuman primates and have developed a protocol for maintaining fear-potentiated startle over repeated sessions with minimal extinction to allow measurement of pharmacological effects on fear-potentiated startle by using within-subjects designs in relatively small groups of monkeys.
A novel, within-subjects testing protocol was used to examine the effects of three compounds in rhesus monkeys that have anxiolytic effects in rodents on fear-potentiated startle but that differ in their mechanism of action. Spontaneous vocalizations during testing also were recorded. Juvenile monkeys that were trained to associate a visual stimulus with a fear-inducing air blast to the face were tested after acute administration of different doses of buspirone diazepam, morphine, or vehicle.
Monkeys rapidly developed a robust and persistent elevation of startle response in the presence of the CS during repeated testing sessions. Diazepam and morphine produced dose-related reductions of fear-potentiated startle. Buspirone did not significantly reduce fear-potentiated startle at the doses tested, although a trend was evident at the highest dose. All drugs reduced rates of coo vocalizations during startle testing.
These fear-potentiated startle results suggest that rhesus monkeys have a pharmacological profile with respect to these compounds that is closer to humans than to rats. This demonstrates the value of examining the effects of drugs on fear-potentiated startle in nonhuman primates.
厌恶感觉刺激对听觉惊吓反应的调节是啮齿动物和人类情绪的一种简单而客观的指标，对于分析与恐惧和焦虑相关的神经系统极具价值。我们已经描述了一种用于测量非人类灵长类动物恐惧增强的全身听觉惊吓的范式，并开发了一种方案，可在重复实验中维持恐惧增强的惊吓反应，且消退最小，从而能够在相对较小的猴子群体中采用受试者内设计来测量药物对恐惧增强惊吓反应的影响。
采用一种新颖的受试者内测试方案，来检验三种在啮齿动物中具有抗焦虑作用但作用机制不同的化合物对恒河猴恐惧增强惊吓反应的影响。测试期间的自发发声也被记录下来。对经过训练将视觉刺激与面部恐惧诱发气吹联系起来的幼年猴子，在急性给予不同剂量的丁螺环酮、地西泮、吗啡或赋形剂后进行测试。
在重复测试期间，猴子在条件刺激存在时迅速产生了强烈且持续的惊吓反应增强。地西泮和吗啡产生了与剂量相关的恐惧增强惊吓反应降低。在所测试的剂量下，丁螺环酮并未显著降低恐惧增强的惊吓反应，尽管在最高剂量时有明显趋势。所有药物都降低了惊吓测试期间咕咕叫声的发生率。
这些恐惧增强惊吓反应的结果表明，恒河猴对这些化合物的药理学特征与人类更为接近，而与大鼠不同。这证明了在非人类灵长类动物中研究药物对恐惧增强惊吓反应影响的价值。
