Bouchekioua Youcef, Nishitani Naoya, Ohmura Yu
Department of Neuropharmacology, Hokkaido University Faculty and Graduate School of Medicine, Sapporo, Japan.
Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Bio Protoc. 2022 Dec 5;12(23). doi: 10.21769/BioProtoc.4568.
Pavlovian fear conditioning is a widely used procedure to assess learning and memory processes that has also been extensively used as a model of post-traumatic stress disorder (PTSD). Freezing, the absence of movement except for respiratory-related movements, is commonly used as a measure of fear response in non-human animals. However, this measure of fear responses can be affected by a different baseline of locomotor activity between groups and/or conditions. Moreover, fear conditioning procedures are usually restricted to a single conditioned stimulus (e.g., a tone cue, the context, etc.) and thus do not depict the complexity of real-life situations where traumatic memories are composed of a complex set of stimuli associated with the same aversive event. To overcome this issue, we use a conditioned lick suppression paradigm where water-deprived mice are presented with a single conditioned stimulus (CS, a tone cue or the context) previously paired with an unconditioned stimulus (US, a foot shock) while consuming water. We use the ratio of number of licks before and during the CS presentation as a fear measure, thereby neutralizing the potential effect of locomotor activity in fear responses. We further implemented the conditioned lick suppression ratio to assess the effect of cue competition using a compound of contextual and tone cue conditioned stimuli that were extinguished separately. This paradigm should prove useful in assessing potential therapeutics and/or behavioral therapies in PTSD, while neutralizing potential confounding effects between locomotor activity and fear responses on one side, and by considering potential cue-competition effects on the other side. Transl Psychiatry (2022), DOI: 10.1038/s41398-022-01815-2 Graphical abstract Illustration reproduced from Bouchekioua et al. (2022).
巴甫洛夫恐惧条件反射是一种广泛用于评估学习和记忆过程的程序，也被广泛用作创伤后应激障碍（PTSD）的模型。静止不动，即除了与呼吸相关的运动外没有其他运动，通常被用作非人类动物恐惧反应的一种测量指标。然而，这种恐惧反应的测量可能会受到不同组和/或条件之间运动活动基线差异的影响。此外，恐惧条件反射程序通常仅限于单个条件刺激（例如，一个音调线索、环境等），因此无法描绘现实生活中创伤性记忆由与同一厌恶事件相关的一组复杂刺激组成的复杂性。为了克服这个问题，我们使用了一种条件性舔舐抑制范式，即给缺水的小鼠呈现一个先前与非条件刺激（US，足部电击）配对的单个条件刺激（CS，一个音调线索或环境），同时小鼠正在饮水。我们使用CS呈现之前和期间的舔舐次数比作为恐惧测量指标，从而消除运动活动对恐惧反应的潜在影响。我们进一步采用条件性舔舐抑制比来评估线索竞争的影响，使用分别消退的环境和音调线索条件刺激的复合物。这种范式应该被证明在评估PTSD的潜在治疗方法和/或行为疗法方面是有用的，一方面消除运动活动和恐惧反应之间的潜在混杂效应，另一方面考虑潜在的线索竞争效应。《转化精神病学》（2022年），DOI: 10.1038/s41398-022-01815-2 图形摘要 插图改编自布谢基瓦等人（2022年）。
