The endocannabinoid (eCB) system is a potential target for the treatment of symptoms of post-traumatic stress disorder (PTSD). Similar to clinical PTSD, approximately 25-30% of rats that undergo cued fear conditioning exhibit impaired extinction learning. In addition to extinction-resistant fear, these "weak extinction" (WE) rats show persistent anxiety-like behaviors. The goal of the present study was to test the hypothesis that behavioural differences between WE animals and those presenting normal extinction patterns (strong extinction; SE) could be mediated by the eCB system. Rats undergoing fear conditioning/extinction and fear recall sessions were initially segregated in weak and strong-extinction groups. Two weeks later, animals underwent a fear recall session followed by a novelty-suppressed feeding (NSF) test. In acute experiments, WE rats were injected with either the fatty acid amide hydrolase (FAAH) inhibitor URB597 or the CB1 agonist WIN55,212-2 1 h prior to long-term recall and NSF testing. SE animals were injected with the inverse CB1 receptor agonist AM251. In chronic experiments, WE and SE rats were given daily injections of URB597 or AM251 between short and long-term recall sessions. We found that acute administration of WIN55,212-2 but not URB597 reduced anxiety-like behaviour in WE rats. In contrast, AM251 was anxiogenic in SE animals. Neither treatment was effective in altering freezing expression during fear recall. The chronic administration of AM251 to SE or URB597 to WE did not alter fear or anxiety-like behaviour or changed the expression of FAAH and CB1. Together, these results suggest that systemic manipulations of the eCB system may alter anxiety-like behaviour but not the behavioural expression of an extinction-resistant associative fear memory.

中文翻译：

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在创伤后应激障碍的啮齿动物模型中，内源性大麻素调节药物可改善焦虑，但不能改善条件恐惧的表达。

内源性大麻素（eCB）系统是治疗创伤后应激障碍（PTSD）症状的潜在目标。与临床PTSD相似，经历暗示恐惧条件的大鼠中约有25％至30％表现出灭绝学习受损。除了抗灭绝的恐惧外，这些“弱灭绝”（WE）大鼠还表现出持续的焦虑样行为。本研究的目的是检验以下假设：WEC动物与表现出正常灭绝模式（强灭绝； SE）的动物之间的行为差​​异可以通过eCB系统介导。最初将经历恐惧条件适应/灭绝和恐惧回忆会议的大鼠分为弱和强灭绝组。两周后，对动物进行恐惧回想，然后进行新奇抑制喂养（NSF）测试。在急性实验中，在进行长期召回和NSF测试之前1小时，WE大鼠被注射了脂肪酸酰胺水解酶（FAAH）抑制剂URB597或CB1激动剂WIN55,212-2。向SE动物注射反向CB1受体激动剂AM251。在慢性实验中，在短期和长期召回之间，每天给WE和SE大鼠注射URB597或AM251。我们发现急性给药WIN55,212-2而不是URB597可以减少WE大鼠的焦虑样行为。相反，AM251在SE动物中具有焦虑作用。恐惧回想期间，两种方法都不能有效地改变冻结表达。AM251对SE或URB597对WE的长期给药并未改变恐惧或焦虑样行为，也未改变FAAH和CB1的表达。一起，