Endocannabinoid modulating drugs improve anxiety but not the expression of conditioned fear in a rodent model of post-traumatic stress disorder

NEUROPHARMACOLOGY

卷:166

Article

Vimalanathan, Akshayan^1,2  Gidyk, Darryl C.¹  Diwan, Mustansir¹  Gouveia, Flavia, V¹  Lipsman, Nir¹  Giacobbe, Peter¹  Nobrega, Jose N.²  Hamani, Clement^1,2 

[1] Sunnybrook Hlth Sci Ctr, Harquail Ctr Neuromodulat, Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada

[2] Ctr Addict & Mental Hlth, Res Imaging Ctr, Behav Neurobiol Lab, 250 Coll St, Toronto, ON M5T 1R8, Canada

关键词: PTSD;    Endocannabinoids;    Animal models;    Fear extinction;    Anxiety;   

DOI  :  10.1016/j.neuropharm.2020.107965

来源: Elsevier

【 摘 要 】

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 CB, 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.

【 授权许可】

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