Document Detail


The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system.
MedLine Citation:
PMID:  23298518     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1-selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.
Authors:
Alline C Campos; Zaira Ortega; Javier Palazuelos; Manoela V Fogaça; Daniele C Aguiar; Javier Díaz-Alonso; Silvia Ortega-Gutiérrez; Henar Vázquez-Villa; Fabricio A Moreira; Manuel Guzmán; Ismael Galve-Roperh; Francisco S Guimarães
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  -     ISSN:  1469-5111     ISO Abbreviation:  Int. J. Neuropsychopharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-13     Citation Subset:  -    
Affiliation:
Department of Pharmacology, School of Medicine of Ribeirão Preto, Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
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