Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways
| Autor: | David Martín-Hernández, Angel Pazos, Elena Castro, Álvaro Díaz, Eva Florensa-Zanuy, Fuencisla Pilar-Cuéllar, Emilio Garro-Martínez, Karina S. Mac-Dowell, Albert Adell |
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| Přispěvatelé: | Universidad de Cantabria, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Salud Mental (España) |
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Kynurenine pathway Hippocampus Antidepressant Pharmacology Biochemistry NF-ĸB Mice 03 medical and health sciences chemistry.chemical_compound cannabidiol 0302 clinical medicine medicine Animals Cannabidiol Kynurenine IL-6 antidepressant Depression business.industry Antidepressive Agents Tail suspension test kynurenine IκBα 030104 developmental biology Hindlimb Suspension chemistry 030220 oncology & carcinogenesis Serotonin Inflammation Mediators business medicine.drug |
| Zdroj: | Biochem Pharmacol . 2021 Mar;185:114433 UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) Digital.CSIC. Repositorio Institucional del CSIC instname Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) |
| Popis: | 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-ĸB, IκBα and PPARγ levels were analyzed by western blot in nuclear and cytosolic fractions of cortical samples. IL-6 and TNFα 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 open-field test. CBD diminished cortical NF-ĸB 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-ĸB 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. This research was supported by the Ministerio de Economía y Competitividad (SAF2015-67457-R MINECO/FEDER), the Ministerio de Ciencia, Innovacion ´ y Universidades (RTI2018-097534-B-I00), the Instituto de Salud Carlos III (PI19/00170), and Centro de Investigacion ´ Biom´edica en Red de Salud Mental (CIBERSAM). E F-Z was supported by a predoctoral fellowship from the Universidad de Cantabria (Spain). |
| Databáze: | OpenAIRE |
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