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Effects of cannabidiol plus sertraline on behavioural and gene expression alterations in a long-lasting animal model of post-traumatic stress disorder
  • Ani Gasparyan,
  • Francisco Navarrete,
  • Jorge Manzanares
Ani Gasparyan
Universidad Miguel Hernandez de Elche - Campus San Juan de Alicante
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Francisco Navarrete
Universidad Miguel Hernández
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Jorge Manzanares
Universidad Miguel Hernandez de Elche - Campus San Juan de Alicante
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Peer review status:UNDER REVIEW

01 Apr 2020Submitted to British Journal of Pharmacology
02 Apr 2020Assigned to Editor
02 Apr 2020Submission Checks Completed
23 May 2020Reviewer(s) Assigned
19 Jun 2020Review(s) Completed, Editorial Evaluation Pending

Abstract

Background and purpose. This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioural and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). Experimental approach. C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate and unpredictable stressful stimuli. Fear-related memory and anxiety-like behaviours were evaluated. The effects of the administration of CBD (20 mg·kg-1, i.p.) and/or STR (10 mg·kg-1, p.o.) were analysed on behavioural and gene expressions changes induced by the model of PTSD. Gene expression changes of targets related with stress regulation, endocannabinoid and serotonergic systems were analysed by real-time PCR. Key results. Mice exposed to the animal model of PTSD showed increased and long-lasting fear-related memory and anxiety-like behaviours. CBD improved fear extinction and anxiety-like behaviour in PTSD animals significantly potentiated when combined with STR. Gene expression analyses revealed a long-term increase of corticotropin releasing factor (CRF) that was significantly normalized with the combination CBD plus STR. Cannabinoid receptors (CB1r and CB2r) were up regulated in PTSD mice whereas the serotonin transporter (5HTT) was reduced. Interestingly, CBD and STR alone or combined induced a significant and marked increase of 5HTT gene expression. Conclusions and implications. These results reveal the synergistic action of the combination CBD plus STR to enhance fear extinction and reduce anxiety-like behaviours, and to normalize gene expression alterations in the long-lasting animal model of PTSD. Taken together, CBD or the combination with STR deserves to be explored for the treatment of PTSD patients.