Comparison between cannabidiol and sertra⁃line in modulation of post-traumatic stress dis⁃order-like behaviors and fear memory in mice

OBJECTIVE Post-traumatic stress disorder(PTSD)is characterized by poor adapta⁃tion to a traumatic experience and disturbances in fear memory regulation,and currently lacks effective medication.Cannabidiol(CBD)is the primary component of the Cannabis sativa plant;it does not have any psychoactive effects and has been implicated in modulating fear learning in mammals.The present study investigated the effect of CBD on PTSD-like behaviors in a mouse pre-shock model,the effect of CBD in the modulation of trauma-related fear memory,a crucial process leading to core symptoms of PTSD.METHODS Pre-shock model was applied in which mice were submitted to training with two days of 0.8 mA×12 times of foot-shock,and PTSD-like behaviors was evaluated during 3 and 26 d,including freezing time to the conditioned context,open field test,elevated plus maze test and social interaction test.RESULTS CBD(10 mg·kg^(-1))administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory,decreasing anxiety-like behavior,and increasing social interaction behavior.However,sertraline(15 mg·kg^(-1))was only effective when adminis⁃tered throughout the test period.Furthermore,CBD reduced the formation,retrieval,and recon⁃solidation of trauma-related fear memory,whereas sertraline only reduced fear-memory retrieval.Neither CBD nor sertraline influenced the acquisi⁃tion of trauma-related fear memory.CONCLU⁃SION CBD produced anti-PTSD-like actions in mice,and could disrupt trauma-related fear mem⁃ory by interfering with multiple aspects of fear memory processing in mice.These findings indi⁃cate that CBD may be a promising candidate for treating PTSD.