Institute of Psychology and Behavioral Neuroscience, University of Tsukuba, Ibaraki, Japan.
Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Osaka, Japan.
Neuropsychopharmacol Rep. 2022 Dec;42(4):521-525. doi: 10.1002/npr2.12287. Epub 2022 Aug 12.
Caffeine is the most widely consumed psychostimulant drug which could affect learning and memory acting through central adenosine receptors. Although caffeine has been suggested to impair the acquisition and the expression of auditory fear conditioning, its effect on the extinction has not been elucidated. To address this issue, in the present study, we investigated whether caffeine affects the extinction of conditioned fear in an auditory fear conditioning paradigm. During conditioning, rats received pairings of auditory cues (conditioned stimulus, CS) and foot shocks (unconditioned stimulus). On the next day, the rats were intraperitoneally administrated saline or caffeine (5 or 10 mg/kg) and then subjected to the extinction training, in which CSs were repeatedly presented without the foot shocks. Twenty-four hours later, the rats were re-exposed to the presentations of CSs (retrieval test). We found an acute caffeine administration dose-dependently decreased freezing rates during the presentations of CS in the extinction training. Furthermore, caffeine-treated animals showed lower conditioned freezing responses in the retrieval test. These findings suggest that caffeine facilitates the extinction of conditioned fear.
咖啡因是最广泛使用的精神兴奋剂药物,它可以通过中枢腺苷受体影响学习和记忆。虽然咖啡因已被认为会损害听觉恐惧条件反射的获得和表达,但它对消退的影响尚未阐明。为了解决这个问题,在本研究中,我们研究了咖啡因是否会影响听觉恐惧条件反射消退范式中的条件性恐惧的消退。在条件反射期间,大鼠接受听觉线索(条件刺激,CS)和足部电击(非条件刺激)的配对。第二天,大鼠腹腔内给予生理盐水或咖啡因(5 或 10mg/kg),然后进行消退训练,其中 CS 反复呈现而没有足部电击。24 小时后,大鼠重新暴露于 CS 的呈现(检索测试)。我们发现,急性咖啡因给药剂量依赖性地降低了消退训练中 CS 呈现时的冻结率。此外,咖啡因处理的动物在检索测试中表现出较低的条件性冻结反应。这些发现表明咖啡因促进了条件性恐惧的消退。