Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Learn Mem. 2010 Jun 1;17(6):306-13. doi: 10.1101/lm.1794710. Print 2010 Jun.
Previous studies suggested that the beta-adrenergic receptor antagonist propranolol might be a novel, potential treatment for post-traumatic stress disorder (PTSD). This hypothesis stemmed mainly from rodent studies showing that propranolol interferes with the reconsolidation of Pavlovian fear conditioning (FC). However, subsequent investigations in humans have produced controversial evidence about the effect of propranolol on fear memories and an effect on PTSD symptomatology has yet to be reported. Thus, it remains to be established whether propranolol interferes with the reconsolidation of fear memories at large. To address this question, we tested the effect of systemic injections of propranolol administered before or after the retrieval of an inhibitory avoidance (IA) memory elicited with different footshock intensities. In parallel, the same treatment was tested on the reconsolidation of Pavlovian FC. Propranolol showed no effect on the reconsolidation of IA, although the pre-retrieval administration resulted in a significant retrieval impairment. This impairment was transient, and memory returned to control levels at later times. In agreement with previous studies, we found that systemic administration of propranolol disrupts the reconsolidation of Pavlovian FC and that its injection following a retrieval elicited by cue exposure also interferes with the reconsolidation of contextual FC. Hence, propranolol disrupts the reconsolidation of Pavlovian FC, but has no effect on the reconsolidation of IA. The results indicate that the efficacy of systemic administration of propranolol in disrupting the reconsolidation of fear memories is limited.
先前的研究表明,β-肾上腺素能受体拮抗剂普萘洛尔可能是一种新颖的、有潜力的创伤后应激障碍(PTSD)治疗方法。这一假说主要源于啮齿动物研究,表明普萘洛尔干扰了条件性恐惧(FC)的再巩固。然而,随后在人类中的研究对普萘洛尔对恐惧记忆的影响产生了有争议的证据,并且尚未报道其对 PTSD 症状的影响。因此,普萘洛尔是否会干扰恐惧记忆的再巩固仍有待确定。为了解决这个问题,我们测试了在不同足底电击强度引发的抑制性回避(IA)记忆检索之前或之后系统注射普萘洛尔对记忆再巩固的影响。同时,对 Pavlovian FC 的再巩固也进行了同样的处理。普萘洛尔对 IA 的再巩固没有影响,尽管在检索前给药会导致明显的检索损伤。这种损伤是短暂的,记忆在以后的时间会恢复到对照水平。与先前的研究一致,我们发现,系统给予普萘洛尔会破坏 Pavlovian FC 的再巩固,并且在通过线索暴露引发检索后给予其注射也会干扰上下文 FC 的再巩固。因此,普萘洛尔会破坏 Pavlovian FC 的再巩固,但对 IA 的再巩固没有影响。结果表明,普萘洛尔系统给药在破坏恐惧记忆的再巩固方面的疗效有限。