Lin Hui-Ching, Mao Sheng-Chun, Gean Po-Wu
Institute of Basic Medical Sciences and Department of Pharmacology, National Cheng-Kung University, Tainan, Taiwan.
Learn Mem. 2006 May-Jun;13(3):316-21. doi: 10.1101/lm.217006. Epub 2006 May 16.
The cannabinoid CB1 receptor has been shown to be critically involved in the extinction of fear memory. Systemic injection of a CB1 receptor antagonist prior to extinction training blocked extinction. Conversely, administration of the cannabinoid uptake inhibitor AM404 facilitated extinction in a dose-dependent manner. Here we show that bilateral infusion of CB1 receptor agonists into the amygdala after memory reactivation blocked reconsolidation of fear memory measured with fear-potentiated startle. The effect was dose-dependent and could be blocked by AM251, a specific CB1 receptor antagonist. In contrast, the effect of CB1 agonists on reconsolidation was no longer seen if memory reactivation was omitted. Concomitant with block of reconsolidation, CB1 agonist-treated animals did not exhibit shock-induced reinstatement or spontaneous recovery of fear. The absence of recovery was not attributable to permanent damage to the amygdala in WIN-treated rats, nor did the effect result from alteration of baseline startle or shock reactivity. These results suggest that CB1 agonists could impair fear memory via blocking reconsolidation.
大麻素CB1受体已被证明在恐惧记忆的消退中起关键作用。在消退训练前全身注射CB1受体拮抗剂可阻断消退。相反，给予大麻素摄取抑制剂AM404以剂量依赖的方式促进了消退。在此我们表明，记忆重新激活后向杏仁核双侧注入CB1受体激动剂可阻断通过恐惧增强惊吓测量的恐惧记忆的重新巩固。该效应具有剂量依赖性，并且可被特异性CB1受体拮抗剂AM251阻断。相比之下，如果省略记忆重新激活，则不再能看到CB1激动剂对重新巩固的作用。与重新巩固的阻断相伴，经CB1激动剂处理的动物未表现出电击诱导的恐惧恢复或恐惧的自发恢复。恐惧恢复的缺失并非归因于经WIN处理的大鼠杏仁核的永久性损伤，该效应也不是由基线惊吓或电击反应性的改变所致。这些结果表明，CB1激动剂可能通过阻断重新巩固来损害恐惧记忆。
