CB1受体拮抗剂AM251会损害大鼠基底外侧杏仁核中巴甫洛夫恐惧记忆的重新巩固。
The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.
作者信息
Ratano Patrizia, Everitt Barry J, Milton Amy L
机构信息
1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK.
出版信息
Neuropsychopharmacology. 2014 Oct;39(11):2529-37. doi: 10.1038/npp.2014.103. Epub 2014 May 7.
We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.
我们通过在记忆重新激活时将CB1受体拮抗剂AM251或脂肪酸酰胺水解酶（FAAH）抑制剂URB597直接注入基底外侧杏仁核（BLA），研究了CB1受体信号传导在先前巩固的听觉恐惧记忆重新巩固中的必要性。AM251破坏了记忆的再稳定，但仅在重新激活后给药时才会如此。URB597在重新激活后给药时会产生轻微、短暂的记忆再稳定增强作用。在重新激活时共同给予GABAA受体拮抗剂荷包牡丹碱可挽救AM251的遗忘效应，这表明重新巩固的破坏是由BLA中GABA能传递的改变介导的。这些数据表明，BLA中的内源性大麻素系统是恐惧记忆重新巩固的重要调节因子，其对记忆的影响是通过与GABA能系统的相互作用介导的。因此，靶向内源性大麻素系统可能具有治疗潜力，以减少创伤后应激障碍等神经精神疾病中适应不良记忆的影响。
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