Pickens Charles L, Golden Sam A, Adams-Deutsch Tristan, Nair Sunila G, Shaham Yavin
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
Biol Psychiatry. 2009 May 15;65(10):881-6. doi: 10.1016/j.biopsych.2008.12.010. Epub 2009 Jan 23.
In 1937, Diven reported that human fear responses to cues previously paired with shock progressively increase or incubate over 24 hours. Since then, fear incubation has been demonstrated in both humans and nonhumans. However, the difficulty of demonstrating long-lasting fear incubation in rodents has hampered the study of the underlying mechanisms of this incubation. Here, we describe a rat procedure where fear reliably incubates over time.
We trained food-restricted rats to lever-press for food pellets in daily 90-min sessions. We then gave each rat 100 30-sec tones co-terminating with a .5-sec .5-mA footshock over 10 days (10 pairings/day). Groups of rats (n = 10-15) were then given four presentations of the tone (the fear cue) 2, 15, 31, or 61 days after fear conditioning training and were assessed for conditioned suppression of lever-pressing.
We found that conditioned fear responses were significantly higher 31 and 61 days after fear training than after 2 or 15 days. In control experiments, we showed that extensive tone-shock pairing is necessary for the emergence of fear incubation and that it is unlikely that non-associative factors contribute to this incubation.
We describe a procedure for generating reliable and long-lasting conditioned fear incubation. Our procedure can be used to study mechanisms of fear incubation and might provide a model for studying the mechanisms of delayed-onset posttraumatic stress disorder that occur in a sub-population of people previously exposed to chronic stressors.
1937年，迪文报告称，人类对先前与电击配对的线索的恐惧反应在24小时内会逐渐增强或潜伏期延长。从那时起，恐惧潜伏期在人类和非人类中均得到了证实。然而，在啮齿动物中证明长期恐惧潜伏期的困难阻碍了对这种潜伏期潜在机制的研究。在此，我们描述了一种大鼠实验程序，通过该程序恐惧能够随时间可靠地潜伏期延长。
我们训练食物受限的大鼠在每天90分钟的实验时段内按压杠杆以获取食物颗粒。然后，在10天内（每天10次配对），给每只大鼠施加100次持续30秒的音调，每次音调结束时伴有0.5秒的0.5毫安足部电击。然后，在恐惧条件训练后的第2、15、31或61天，对几组大鼠（每组n = 10 - 15只）进行4次音调（恐惧线索）呈现，并评估杠杆按压的条件性抑制情况。
我们发现，恐惧训练后31天和61天的条件性恐惧反应显著高于2天或15天后的反应。在对照实验中，我们表明广泛的音调 - 电击配对是恐惧潜伏期出现所必需的，并且非联想因素不太可能导致这种潜伏期延长。
我们描述了一种产生可靠且持久的条件性恐惧潜伏期延长的程序。我们的程序可用于研究恐惧潜伏期的机制，并可能为研究先前暴露于慢性应激源的亚人群中发生的延迟性创伤后应激障碍的机制提供一个模型。
