Journal
BIOCHEMICAL PHARMACOLOGY
Volume 185, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114433
Keywords
Cannabidiol; Antidepressant; Kynurenine; IL-6; NF-?B
Categories
Funding
- Ministerio de Economia y Competitividad [SAF2015-67457-R MINECO/FEDER]
- Ministerio de Ciencia, Innovacion y Universidades [RTI2018-097534-B-I00]
- Instituto de Salud Carlos III [PI19/00170]
- Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM)
- Universidad de Cantabria (Spain)
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Recent evidence suggests that cannabidiol (CBD) has antidepressant properties in a neuroinflammatory model of depression, reducing inflammatory mediators and the activation of specific pathways.
Major Depression is a severe psychiatric condition with a still poorly understood etiology. In the last years, evidence supporting the neuroinflammatory hypothesis of depression has increased. In the current clinical scenario, in which the available treatments for depression is far from optimal, there is an urgent need to develop fast-acting drugs with fewer side effects. In this regard, recent pieces of evidence suggest that cannabidiol (CBD), the major non-psychotropic component of Cannabis sativa with anti-inflammatory properties, appears as a drug with antidepressant properties. In this work, CBD 30 mg/kg was administered systemically to mice 30 min before lipopolysaccharide (LPS; 0.83 mg/kg) administration as a neuroinflammatory model, and behavioral tests for depressive-, anhedonic- and anxious-like behavior were performed. NF-?B, I?B? and PPAR? levels were analyzed by western blot in nuclear and cytosolic fractions of cortical samples. IL-6 and TNF? levels were determined in plasma and prefrontal cortex using ELISA and qPCR techniques, respectively. The precursor tryptophan (TRP), and its metabolites kynurenine (KYN) and serotonin (5-HT) were measured in hippocampus and cortex by HPLC. The ratios KYN/TRP and KYN/5-HT were used to estimate indoleamine 2,3-dioxygenase (IDO) activity and the balance of both metabolic pathways, respectively. CBD reduced the immobility time in the tail suspension test and increased sucrose preference in the LPS model, without affecting locomotion and central activity in the openfield test. CBD diminished cortical NF-?B activation, IL-6 levels in plasma and brain, and the increased KYN/TRP and KYN/5-HT ratios in hippocampus and cortex in the LPS model. Our results demonstrate that CBD produced antidepressant-like effects in the LPS neuroinflammatory model, associated to a reduction in the kynurenine pathway activation, IL-6 levels and NF-?B activation. As CBD stands out as a promising antidepressant drug, more research is needed to completely understand its mechanisms of action in depression linked to inflammation.
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