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Cannabinoids prevent depressive‐like symptoms and alterations in BDNF expression in a rat model of PTSD

Or Burstein,Noa Shoshan,Ravid Doron,I. Akirav

Published 2018 in Progress in Neuro-psychopharmacology and Biological Psychiatry

ABSTRACT

ABSTRACT Posttraumatic stress disorder (PTSD) is a debilitating condition highly comorbid with depression. The endocannabinoid (eCB) system and brain‐derived neurotrophic factor (BDNF) are suggestively involved in both disorders. We examined whether cannabinoids can prevent the long‐term depressive‐like symptoms induced by exposure to the shock and situational reminders (SRs) model of PTSD. The CB1/2 receptor agonist WIN55,212–2 (0.5mg/kg; i.p.), the fatty acid hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.) or vehicle were administered 2h after severe shock. Cannabinoids prevented the shock/SRs‐induced alterations in social recognition memory, locomotion, passive coping, anxiety‐like behavior, anhedonia, fear retrieval, fear extinction and startle response as well as the decrease in BDNF levels in the hippocampus and prefrontal cortex (PFC). Furthermore, significant correlations were found between depressive‐like behaviors and BDNF levels in the brain. The findings suggest that cannabinoids may prevent both depressive‐ and PTSD‐like symptoms following exposure to severe stress and that alterations in BDNF levels in the brains' fear circuit are involved in these effects. HIGHLIGHTSThe shock and reminders model of PTSD resulted in depression‐like symptoms.Cannabinoid agents administered 2h after shock exposure prevented these symptoms.Symptoms were correlated with BDNF expression in the fear and reward circuit.Cannabinoids may prevent and treat PTSD‐depression comorbidity after severe stress.

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